vesicular transport adaptor proteins

Summary

Summary: A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.

Top Publications

  1. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
  2. ncbi Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
  3. ncbi Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis
    H Chen
    Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nature 394:793-7. 1998
  4. pmc MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:5102-14. 2003
  5. ncbi Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains
    M Yamabhai
    Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706 1532, USA
    J Biol Chem 273:31401-7. 1998
  6. ncbi Curvature of clathrin-coated pits driven by epsin
    Marijn G J Ford
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 419:361-6. 2002
  7. pmc The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15
    A S Sengar
    Programs of Cancer and Blood Research, and Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada
    EMBO J 18:1159-71. 1999
  8. ncbi Interaction of tyrosine-based sorting signals with clathrin-associated proteins
    H Ohno
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 269:1872-5. 1995
  9. ncbi Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor
    E C Dell'Angelica
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell 3:11-21. 1999
  10. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004

Research Grants

Detail Information

Publications265 found, 100 shown here

  1. ncbi IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Nat Immunol 4:491-6. 2003
    ..Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response...
  2. ncbi Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
    ..These findings demonstrate that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense...
  3. ncbi Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis
    H Chen
    Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Nature 394:793-7. 1998
    ..We propose that epsin may participate, together with Eps15, in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission...
  4. pmc MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:5102-14. 2003
    ..Our results indicate that MO25 may function as a scaffolding component of the LKB1-STRAD complex and plays a crucial role in regulating LKB1 activity and cellular localization...
  5. ncbi Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains
    M Yamabhai
    Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706 1532, USA
    J Biol Chem 273:31401-7. 1998
    ..We propose that Intersectin is a component of the endocytic machinery...
  6. ncbi Curvature of clathrin-coated pits driven by epsin
    Marijn G J Ford
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 419:361-6. 2002
    ..We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations...
  7. pmc The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15
    A S Sengar
    Programs of Cancer and Blood Research, and Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada
    EMBO J 18:1159-71. 1999
    ..The Ese1-Eps15 scaffold therefore links dynamin, epsin and other endocytic pathway components...
  8. ncbi Interaction of tyrosine-based sorting signals with clathrin-associated proteins
    H Ohno
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Science 269:1872-5. 1995
    ..The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery...
  9. ncbi Altered trafficking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the beta 3A subunit of the AP-3 adaptor
    E C Dell'Angelica
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell 3:11-21. 1999
    ..Our results suggest that AP-3 functions in protein sorting to lysosomes and provide an example of a human disease in which altered trafficking of integral membrane proteins is due to mutations in a component of the sorting machinery...
  10. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  11. ncbi Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP
    N K Hussain
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada
    Nat Cell Biol 3:927-32. 2001
    ..These studies reveal a role for intersectin-l in a novel mechanism of N-WASP activation and in regulation of the actin cytoskeleton...
  12. ncbi A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction
    G Pelicci
    Istituto Clinica Medica I, Policlinico Monteluce, University of Perugia, Italy
    Cell 70:93-104. 1992
    ..These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells...
  13. ncbi Adaptors for clathrin coats: structure and function
    David J Owen
    Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 2XY, UK
    Annu Rev Cell Dev Biol 20:153-91. 2004
    ..This review focuses on the structure of clathrin adaptors and how these structures provide functional information on the mechanism of CCV formation...
  14. ncbi Three-dimensional structure of the complexin/SNARE complex
    Xiaocheng Chen
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Neuron 33:397-409. 2002
    ..These results suggest that complexin stabilizes the fully assembled SNARE complex as a key step that enables the exquisitely high speed of Ca(2+)-evoked neurotransmitter release...
  15. ncbi Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly
    Melissa A Edeling
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom
    Dev Cell 10:329-42. 2006
    ..Another interaction surface on the beta2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lattice edges during assembly...
  16. ncbi Novel human homologues of p47phox and p67phox participate in activation of superoxide-producing NADPH oxidases
    Ryu Takeya
    Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    J Biol Chem 278:25234-46. 2003
    ..Thus, the novel homologues p41nox and p51nox likely function together or in combination with a classical one, thereby activating the two Nox family oxidases...
  17. ncbi A structural explanation for the binding of multiple ligands by the alpha-adaptin appendage domain
    D J Owen
    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Cell 97:805-15. 1999
    ..A single site for binding multiple ligands would allow for temporal and spatial regulation in the recruitment of components of the endocytic machinery...
  18. ncbi TLR signaling pathways
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Semin Immunol 16:3-9. 2004
    ..Thus, TIR domain-containing adaptors provide specificity of TLR signaling...
  19. pmc A family of ADP-ribosylation factor effectors that can alter membrane transport through the trans-Golgi
    A L Boman
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322 3050, USA
    Mol Biol Cell 11:1241-55. 2000
    ....
  20. ncbi Adaptable adaptors for coated vesicles
    Margaret S Robinson
    University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Hills Road, Cambridge, UK CB2 2XY
    Trends Cell Biol 14:167-74. 2004
    ..Adaptors participate in trafficking pathways shared by all cells, and they are also used to generate specialized organelles and to influence cell fate during development...
  21. pmc Characterization of a fourth adaptor-related protein complex
    J Hirst
    University of Cambridge, Department of Clinical Biochemistry and Cambridge Institute for Medical Research, Cambridge CB2 2XY, England
    Mol Biol Cell 10:2787-802. 1999
    ..AP-4 is of relatively low abundance, but it is expressed ubiquitously, suggesting that it participates in a specialized trafficking pathway but one that is required in all cell types...
  22. ncbi Class C Vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion
    T K Sato
    Division of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California at San Diego School of Medicine, La Jolla 92093, USA
    Mol Cell 6:661-71. 2000
    ..Therefore, we propose that the C-Vps complex associates with unpaired (activated) Vam3 to mediate the assembly of trans-SNARE complexes during both vesicle docking/fusion and vacuole-to-vacuole fusion...
  23. ncbi Splice variants of intersectin are components of the endocytic machinery in neurons and nonneuronal cells
    N K Hussain
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada
    J Biol Chem 274:15671-7. 1999
    ..These data suggest that the long and short forms of intersectin are components of the endocytic machinery in neurons and nonneuronal cells...
  24. ncbi Disabled-2 inactivation is an early step in ovarian tumorigenicity
    Z Fazili
    Department of Biochemistry and Winship Cancer Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Oncogene 18:3104-13. 1999
    ..Thus, this study indicates that the loss of Dab2 expression is correlated with tumorigenicity of the cells disregarding the grade of the tumors, and loss of Dab2 expression is an early event in ovarian malignancies...
  25. pmc The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis
    S A Laporte
    Howard Hughes Medical Institute Laboratories and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 96:3712-7. 1999
    ..These findings point to a role for AP-2 in GPCR endocytosis, and they suggest that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes of membrane receptors...
  26. ncbi Mu1B, a novel adaptor medium chain expressed in polarized epithelial cells
    H Ohno
    Department of Molecular Genetics, Chiba University Graduate School of Medicine, Japan
    FEBS Lett 449:215-20. 1999
    ..Yeast two-hybrid analyses show that mu1B is capable of interacting with generic tyrosine-based sorting signals. These observations suggest that mu1B may be involved in protein sorting events specific to polarized cells...
  27. ncbi Role of Drosophila alpha-adaptin in presynaptic vesicle recycling
    M Gonzalez-Gaitan
    Max Planck Institut fur biophysikalische Chemie, Abt Molekulare Entwicklungsbiologie, Gottingen, Germany
    Cell 88:767-76. 1997
    ..Our results suggest an alpha-adaptin-dependent control of the vesicle cycle that maintains the balance between the amount of vesicle- and surface-associated membranes...
  28. ncbi Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes
    M G Ford
    Medical Research Council MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    Science 291:1051-5. 2001
    ..This was shown by using purified components and a budding assay on preformed lipid monolayers. In the presence of AP180, clathrin lattices formed on the monolayer. When AP2 was also present, coated pits were formed...
  29. ncbi EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP
    Fumitoshi Irie
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Neurosci 5:1117-8. 2002
  30. ncbi The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits
    S A Laporte
    Howard Hughes Medical Institute Laboratories and the Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 275:23120-6. 2000
    ..These results reveal that the binding of a receptor-beta-arrestin complex to AP-2, not to clathrin, is necessary for the initial targeting of beta(2)-adrenergic receptor to clathrin-coated pits...
  31. pmc The structure and function of the beta 2-adaptin appendage domain
    D J Owen
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
    EMBO J 19:4216-27. 2000
    ..This results in the displacement of the other ligands from the beta 2 appendage. Thus clathrin binding to an AP2-accessory protein complex would cause the controlled release of accessory proteins at sites of vesicle formation...
  32. ncbi Emerging roles of pseudokinases
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Trends Cell Biol 16:443-52. 2006
    ..We also discuss the emerging functions of other pseudokinases, including HER3 (also called ErbB3), EphB6, CCK4 (also called PTK7), KSR, Trb3, GCN2, TRRAP, ILK and CASK...
  33. ncbi EHSH1/intersectin, a protein that contains EH and SH3 domains and binds to dynamin and SNAP-25. A protein connection between exocytosis and endocytosis?
    M Okamoto
    Center for Basic Neuroscience, Howard Hughes Medical Institute, and the Department of Molecular Genetics, The University of Texas Southwestern Medical School, Dallas Texas 75235, USA
    J Biol Chem 274:18446-54. 1999
    ..The ability of multiple SH3 domains in EHSH1 to bind to dynamin suggests that EHSH1 can cluster several dynamin molecules in a manner that is regulated by alternative splicing...
  34. pmc Arf1p, Chs5p and the ChAPs are required for export of specialized cargo from the Golgi
    Mark Trautwein
    Friedrich Miescher Laboratorium, Max Planck Gesellschaft, Tubingen, Germany
    EMBO J 25:943-54. 2006
    ..In addition, they are all at least partially localized to the TGN in a Chs5p-dependent manner. Most importantly, several ChAPs can interact physically with Chs3p. We propose that the ChAPs facilitate export of cargo out of the Golgi...
  35. ncbi Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
    K Hoebe
    Department of Immunology, IMM 31, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 424:743-8. 2003
    ..This reveals that an alternative MyD88-dependent 'adaptor X' pathway is present in some, but not all, macrophages, and implies afferent immune specialization...
  36. ncbi Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome
    C Pucharcos
    Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Barcelona, Spain
    Eur J Hum Genet 7:704-12. 1999
    ....
  37. ncbi The critical role of Shc in insulin-like growth factor-I-mediated mitogenesis and differentiation in 3T3-L1 preadipocytes
    C M Boney
    Department of Pediatrics Rhode Island Hospital, Providence 02903, USA
    Mol Endocrinol 14:805-13. 2000
    ..Our results suggest that loss of the ability of IGF-I to activate Shc signaling to MAPK may be an early component of adipogenesis in 3T3-L1 cells...
  38. pmc The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein
    M S Nielsen
    Department of Medical Biochemistry and Department of Cell Biology, University of Aarhus, 8000 Aarhus C, Denmark
    EMBO J 20:2180-90. 2001
    ....
  39. pmc The vacuolar kinase Yck3 maintains organelle fragmentation by regulating the HOPS tethering complex
    Tracy J LaGrassa
    Biochemie Zentrum der Universitat Heidelberg, 69120 Heidelberg, Germany
    J Cell Biol 168:401-14. 2005
    ..Because Yck3 also promotes efficient vacuole inheritance, we propose that tethering complex phosphorylation is a part of a general, switch-like mechanism for driving changes in organelle architecture...
  40. pmc Numb is an endocytic protein
    E Santolini
    Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
    J Cell Biol 151:1345-52. 2000
    ..Finally, fragments of Numb act as dominant negatives on both constitutive and ligand-regulated receptor-mediated internalization, suggesting a general role for Numb in the endocytic process...
  41. ncbi The adaptor protein Tks5/Fish is required for podosome formation and function, and for the protease-driven invasion of cancer cells
    Darren F Seals
    Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    Cancer Cell 7:155-65. 2005
    ..Thus, Tks5/Fish appears to be required for podosome formation, for degradation of the extracellular matrix, and for invasion of some cancer cells...
  42. pmc A requirement for epsin in mitotic membrane and spindle organization
    Zhonghua Liu
    Department of Embryology and 2 Howard Hughes Medical Institute, Carnegie Institution of Washington, Baltimore, MD 21218, USA
    J Cell Biol 186:473-80. 2009
    ..Our study of epsin provides evidence that mitotic membrane organization influences spindle integrity...
  43. pmc Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation
    Hua Shen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA
    J Immunol 181:1849-58. 2008
    ..In sum, in our experimental systems, TRIF signaling plays a more important role in LPS-induced macrophage activation than in DC activation...
  44. ncbi Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia
    Stephane Martin
    Institut de Pharmacologie Moleculaire et Cellulaire, Unité Mixte de Recherche 6097 du Centre National de la Recherche Scientifique, Sophia Antipolis, 06560 Valbonne, France
    J Neurosci 23:1198-205. 2003
    ..This demonstrates that the neurotensin receptor-3 is functional and mediates the migratory actions of neurotensin...
  45. ncbi The yeast clathrin adaptor protein complex 1 is required for the efficient retention of a subset of late Golgi membrane proteins
    Raphael H Valdivia
    Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Dev Cell 2:283-94. 2002
    ..Similarly, in AP-1 deficient cells, the resident TGN/early endosome syntaxin, Tlg1p, is missorted. We propose that clathrin and AP-1 act to recycle Chs3p and Tlg1p from the early endosome to the TGN...
  46. ncbi AP-4, a novel protein complex related to clathrin adaptors
    E C Dell'Angelica
    Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 274:7278-85. 1999
    ..We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells...
  47. ncbi A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor
    P A Bresnahan
    Gladstone Institute of Virology and Immunology, University of California, San Francisco 94141, USA
    Curr Biol 8:1235-8. 1998
    ..Our findings also reveal an evolutionary difference between HIV-1 and HIV-2/SIV in which the Nef proteins utilize structurally distinct motifs for binding cellular adaptors...
  48. pmc The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family
    M H Dreyling
    Section of Hematology Oncology, University of Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 93:4804-9. 1996
    ..The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line...
  49. pmc Intersectin regulates fission and internalization of caveolae in endothelial cells
    Sanda A Predescu
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA
    Mol Biol Cell 14:4997-5010. 2003
    ..Taken together, the results indicate the crucial role of intersectin in the mechanism of caveolae fission in endothelial cells...
  50. ncbi Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2
    T Shiratori
    Division of Molecular Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chuo Ku, Japan
    Immunity 6:583-9. 1997
    ..Our results suggest that the phosphorylation state of a single tyrosine residue determines whether CTLA-4 delivers a negative signal or is internalized...
  51. ncbi Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response
    Gagik Oganesyan
    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 609 Charles E Young Dr East, Los Angeles, California 90095, USA
    Nature 439:208-11. 2006
    ..Our data demonstrate that TRAF3 is a major regulator of type I IFN production and the innate antiviral response...
  52. ncbi Genetic analyses of adaptin function from yeast to mammals
    Markus Boehm
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18T Room 101, National Institutes of Health, Bethesda, MD 20892, USA
    Gene 286:175-86. 2002
    ..Here, we review recent progress in the genetic analysis of the function of AP complexes, focusing on studies that make use of targeted interference or naturally-occurring mutations in various model organisms...
  53. pmc STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7
    Julia Dorfman
    Program in Biophysics, Department of Microbiology, University of Virginia School of Medicine, Charlottesville VA 22908 0577, USA
    Mol Biol Cell 19:1614-26. 2008
    ..These results identify a multifactored mechanism to control LKB1 localization, and they suggest that the STRADbeta-LKB1 complex might possess unique functions in the nucleus...
  54. ncbi The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
    Luke A J O'Neill
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
    Nat Rev Immunol 7:353-64. 2007
    ..These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling...
  55. ncbi Sortilin is essential for proNGF-induced neuronal cell death
    Anders Nykjaer
    Department of Medical Biochemistry, Ole Worms Alle 170, Aarhus University, Gustav Wieds Vej 10, DK 8000 Aarhus C, Denmark
    Nature 427:843-8. 2004
    ..Here we report that proNGF creates a signalling complex by simultaneously binding to p75NTR and sortilin. Thus sortilin acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF...
  56. pmc The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin
    Hong Chen
    Department of Cell Biology and Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA
    Proc Natl Acad Sci U S A 102:2766-71. 2005
    ..Our results reveal an important regulatory mechanism in epsin function. The mutually exclusive colocalization of epsin with membrane-bound Ub or clathrin may play a role in controlling the endocytic route taken by ubiquitinated cargo...
  57. pmc TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta
    Jonathan C Kagan
    Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 9:361-8. 2008
    ..Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location...
  58. ncbi Microbial recognition by Toll-like receptors
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    J Dermatol Sci 34:73-82. 2004
    ..TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses...
  59. pmc LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF
    Katherine A Fitzgerald
    Division of Infectious Disease and Immunology, Department of Medicine, The University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Exp Med 198:1043-55. 2003
    ..These studies suggest that TRIF and TRAM both function in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to LPS...
  60. pmc Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42
    Magali Malacombe
    Département Neurotransmission and Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives UMR 7168 LC2, Centre National de la Recherche Scientifique and Université Louis Pasteur, Strasbourg, France
    EMBO J 25:3494-503. 2006
    ..Our results extend the current role of intersectin-1L in endocytosis to a function in exocytosis and support the idea that intersectin-1L is an adaptor that coordinates exo-endocytotic membrane trafficking in secretory cells...
  61. ncbi Disabled-2 is an epithelial surface positioning gene
    Dong Hua Yang
    Ovarian Cancer and Tumor Cell Biology Programs, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 282:13114-22. 2007
    ..Thus, the findings indicate that Dab2 is a surface positioning gene and suggest a novel mechanism of epithelial cell surface targeting...
  62. pmc Yeast epsins contain an essential N-terminal ENTH domain, bind clathrin and are required for endocytosis
    B Wendland
    Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA
    EMBO J 18:4383-93. 1999
    ..Based on these and other data, we propose that the yeast epsin-like proteins are essential components of an endocytic complex that may act at multiple stages in the endocytic pathway...
  63. ncbi The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation
    S O Meakin
    Neurodegeneration Research Group, The John P Robarts Research Institute, London, Ontario N6A 5K8, Canada
    J Biol Chem 274:9861-70. 1999
    ..Importantly, overexpression of FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal differentiation...
  64. pmc EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking
    Ian G Mills
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK
    J Cell Biol 160:213-22. 2003
    ....
  65. ncbi ENTH/ANTH proteins and clathrin-mediated membrane budding
    Valerie Legendre-Guillemin
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
    J Cell Sci 117:9-18. 2004
    ....
  66. pmc Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic
    F Tebar
    Department of Pharmacology, University of Colorado Health Science Center, Denver, Colorado 80111, USA
    Mol Biol Cell 10:2687-702. 1999
    ..Altogether, the data suggest that CALM is an important component of coated pit internalization machinery, possibly involved in the regulation of clathrin recruitment to the membrane and/or the formation of the coated pit...
  67. ncbi Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation
    H Gu
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 2:729-40. 1998
    ..Our results identify p97 as an important regulator of receptor signaling that controls a novel pathway to immediate-early gene activation and suggest multiple functions for SHP2 in cytokine receptor signaling...
  68. ncbi Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis
    C Pucharcos
    Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Avia de Castelldefels Km 2 7, L Hospitalet de Llobregat, 08907, Barcelona, Spain
    FEBS Lett 478:43-51. 2000
    ..Moreover, their overexpression, as well as the corresponding ITSN1 protein forms, inhibits transferrin internalization...
  69. ncbi Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc
    Antonella De Luca
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    J Immunol 179:5999-6008. 2007
    ..This is the first study to show that the same tryptophan catabolites can foster dendritic cell-supported generation of Foxp3(+) cells and mediate, at the same time, inhibition of RORgammat-expressing T cells...
  70. pmc Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 19:5360-72. 2008
    ..These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways...
  71. pmc Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics
    Sylwia Wasiak
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal Quebec H3A 2B4, Canada
    J Cell Biol 158:855-62. 2002
    ..These data suggest a role for enthoprotin in clathrin-mediated budding on internal membranes. Our study reveals the utility of proteomics in the identification of novel vesicle trafficking proteins...
  72. ncbi The molecular machinery for lysosome biogenesis
    C Mullins
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Bioessays 23:333-43. 2001
    ..Other recently identified components, however, appear to be unique to higher eukaryotes. BioEssays 23:333-343, 2001. Published 2001 John Wiley & Sons, Inc...
  73. pmc Amyloid-beta neurotoxicity is mediated by FISH adapter protein and ADAM12 metalloprotease activity
    Nikolay L Malinin
    Elan Pharmaceuticals, 1000 Gateway Boulevard, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 102:3058-63. 2005
    ..These data suggest that Abeta toxicity is mediated by FISH and ADAM12 and may provide insights into therapeutic strategies for AD treatment...
  74. ncbi Evaluation of the role of Disabled-2 in nerve growth factor-mediated neurite outgrowth and cellular signalling
    Ching Hui Huang
    Graduate Institute of Basic Medical Sciences, Chang Gung University, Taoyuan 333, Taiwan, Republic of China
    Cell Signal 19:1339-47. 2007
    ..Together, this study defines a role of DAB2 in the control of neuronal plasticity and demonstrates for the first time that DAB2 is a negative regulator in NGF-mediated neurite outgrowth...
  75. ncbi Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity
    Jacek Jaworski
    Department of Neuroscience, Erasmus Medical Center, 3015 GE, Rotterdam, The Netherlands
    Neuron 61:85-100. 2009
    ....
  76. pmc Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly
    Eva M Schmid
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    PLoS Biol 4:e262. 2006
    ..However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors...
  77. pmc Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly
    L M Traub
    Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:8907-12. 1999
    ....
  78. ncbi The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor
    J Mazella
    Institut de Pharmacologie Moleculaire et Cellulaire, CNRS, UPR 0411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
    J Biol Chem 273:26273-6. 1998
    ..This 100-kDa NT receptor corresponded to the mature form of the receptor. The NT3/gp95/sortilin protein is the first transmembrane neuropeptide receptor that does not belong to the superfamily of G-protein-coupled receptors...
  79. ncbi Identification and characterization of novel clathrin adaptor-related proteins
    H Takatsu
    Institute of Biological Sciences, University of Tsukuba, Tsukuba Science City, Ibaraki 305 8572, Japan
    J Biol Chem 273:24693-700. 1998
    ..These data suggest that gamma2-adaptin constitute a novel adaptor-related complex that participates in a transport step different from that of AP-1...
  80. ncbi A SNARE complex containing syntaxin 3 is present in ribbon synapses of the retina
    C W Morgans
    Department of Neuroanatomy, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany
    J Neurosci 16:6713-21. 1996
    ..Thus, in the retina, expression of syntaxin 3 is correlated with ribbon synapses and may play a role in the tonic release of neurotransmitter...
  81. pmc Molecular evolution of Phox-related regulatory subunits for NADPH oxidase enzymes
    Tsukasa Kawahara
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    BMC Evol Biol 7:178. 2007
    ....
  82. ncbi Adaptors for clathrin-mediated traffic
    T Kirchhausen
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 15:705-32. 1999
    ..This review focuses on the most recent advances dealing with the molecular basis for sorting by clathrin adaptors...
  83. ncbi Life of a clathrin coat: insights from clathrin and AP structures
    Melissa A Edeling
    Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK
    Nat Rev Mol Cell Biol 7:32-44. 2006
    ....
  84. ncbi A role of Toll-IL-1 receptor domain-containing adaptor-inducing IFN-beta in the host response to Pseudomonas aeruginosa lung infection in mice
    Melanie R Power
    Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
    J Immunol 178:3170-6. 2007
    ..aeruginosa from the lung during the initial 24-48 h of infection. Thus, TRIF represents a novel mechanism involved in the development of host response to P. aeruginosa infection...
  85. ncbi Unusual structural organization of the endocytic proteins AP180 and epsin 1
    Christoph Kalthoff
    Department of Cell Biology, Center of Anatomy, Hannover Medical School, D 30125 Hannover, Germany
    J Biol Chem 277:8209-16. 2002
    ....
  86. ncbi Interaction of the cation-dependent mannose 6-phosphate receptor with GGA proteins
    Balraj Doray
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 277:18477-82. 2002
    ..These studies provide an explanation for the observed differences in the relative affinities of the two MPRs for the GGA proteins. Furthermore, they indicate that the GGAs participate in lysosomal enzyme sorting mediated by the CD-MPR...
  87. pmc GGA and Arf proteins modulate retrovirus assembly and release
    Anjali Joshi
    Virus Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702 1201, USA
    Mol Cell 30:227-38. 2008
    ..These findings identify the GGA proteins as modulators of HIV-1 release and the Arf proteins as critical cellular cofactors in retroviral Gag trafficking to the plasma membrane...
  88. pmc Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet
    C E Ooi
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 16:4508-18. 1997
    ..Thus, the eye pigmentation defect in the Drosophila garnet mutant may be attributed to compromised function of a coat protein involved in intracellular transport processes required for biogenesis or function of pigment granules...
  89. ncbi A new member of the amphiphysin family connecting endocytosis and signal transduction pathways
    C Leprince
    INSERM U248, Institut Curie, 26 Rue d Ulm, 75231 Paris Cedex 05, France
    J Biol Chem 272:15101-5. 1997
    ..This hypothesis is strengthened by the ability of BRAMP2 to interact with the p21(ras) exchange factor SOS, in vitro, as a possible point of interconnection between the endocytic and signaling pathways...
  90. ncbi LKB1-dependent signaling pathways
    Dario R Alessi
    Medical Research Council, Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Annu Rev Biochem 75:137-63. 2006
    ..The work described in this review shows how a study of an obscure cancer syndrome can uncover new and important regulatory pathways, relevant to the understanding of multiple human diseases...
  91. ncbi Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells
    Tsukasa Kawahara
    Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
    Am J Physiol Cell Physiol 288:C450-7. 2005
    ..Thus the H. pylori LPS-stimulated O2- production in gastric mucosal cells appears to require two distinct events: 1) transcriptional upregulation of Nox1 and NOXO1 and 2) activation of Rac1...
  92. ncbi The Vps10p-domain receptor family
    Guido Hermey
    Institute of Molecular and Cellular Cognition, Zentrum fur Molekulare Neurobiologie Hamburg, Hamburg, Germany
    Cell Mol Life Sci 66:2677-89. 2009
    ..For instance, it has been demonstrated that Sortilin partakes in the transduction of proapoptotic effects, and there is converging biochemical and genetic evidence that implies that SorLA is an Alzheimer's disease risk factor...
  93. ncbi Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1
    Kei Miyano
    Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
    J Biol Chem 281:21857-68. 2006
    ..Furthermore, a mutant Noxa1 carrying the substitution of Ala for Val-205 in the activation domain, which is expected to undergo a conformational change upon Rac binding, fully localizes to the membrane but fails to activate Nox1...
  94. pmc Chs5/6 complex: a multiprotein complex that interacts with and conveys chitin synthase III from the trans-Golgi network to the cell surface
    Siraprapha Sanchatjate
    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Barker Hall, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Biol Cell 17:4157-66. 2006
    ..Our results suggest a model of protein sorting at the TGN that involves a peripheral, possibly coat, complex that includes multiple related copies of a specificity determining subunit...
  95. pmc Mammalian GGAs act together to sort mannose 6-phosphate receptors
    Pradipta Ghosh
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 163:755-66. 2003
    ..The morphology of the TGN was also altered. These findings indicate that the three mammalian GGAs cooperate to sort cargo and are required for maintenance of TGN structure...
  96. pmc Pho86p, an endoplasmic reticulum (ER) resident protein in Saccharomyces cerevisiae, is required for ER exit of the high-affinity phosphate transporter Pho84p
    W T Lau
    Program in Biophysics, University of California, San Francisco, CA 94143 0448, USA
    Proc Natl Acad Sci U S A 97:1107-12. 2000
    ..Interestingly, the requirement of Pho86p for ER exit is specific to Pho84p, because other members of the hexose transporter family to which Pho84 belongs are not mislocalized in the absence of Pho86p...
  97. ncbi Proapoptotic signalling through Toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells
    A Weber
    Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany
    Cell Death Differ 17:942-51. 2010
    ..These results indicate that the proapoptotic activity of TLR3/TRIF/caspase-8 in melanoma cells is under the control of IAPs, and the use of novel Smac mimetics might be a feasible approach to target melanoma...
  98. ncbi Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains
    Saurav Misra
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 415:933-7. 2002
    ..The rigid spatial alignment of the three binding subsites leads to high specificity...
  99. ncbi Synaptotagmin I is a high affinity receptor for clathrin AP-2: implications for membrane recycling
    J Z Zhang
    Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235
    Cell 78:751-60. 1994
    ..Thus, synaptotagmin I may be a multifunctional protein with a function in endocytosis in addition to the previously proposed role in exocytosis...
  100. ncbi Deficiencies in subunits of the Conserved Oligomeric Golgi (COG) complex define a novel group of Congenital Disorders of Glycosylation
    Renate Zeevaert
    Center for Human Genetics, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven, Belgium
    Mol Genet Metab 93:15-21. 2008
    ..Among 35 CDG-II patients we found 5 patients with a COG defect. COG defects are a novel group of CDG-II with deficient N- as well as O-glycosylation...
  101. ncbi Clathrin and adaptors
    J Hirst
    Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, UK
    Biochim Biophys Acta 1404:173-93. 1998
    ..Genetic studies indicate that AP-3 plays a role in the sorting of proteins to lysosomes and lysosome-related organelles...

Research Grants62

  1. Internalization of gap junctions as a regulatory mechanism of direct GJIC
    Matthias M Falk; Fiscal Year: 2013
    ....
  2. MOLECULAR STUDIES OF SELECTIVE PROTEIN TRANSPORT
    Gregory S Payne; Fiscal Year: 2013
    ....
  3. Regulation of Protease-activated Receptor-1 Signaling
    JoAnn Trejo; Fiscal Year: 2012
    ..Thus, understanding protease-activated receptor-1 signaling, and developing the ability to manipulate it, may provide new strategies for the prevention and treatment of thrombin-related vascular diseases. ..
  4. SORTING OF PLASMA MEMBRANE PROTEINS IN EPITHELIAL CELLS
    ENRIQUE J RODRIGUEZ-BOULAN; Fiscal Year: 2013
    ..The studies proposed will contribute to a deeper understanding of epithelial trafficking mechanisms, which, in turn, is likely to help understand and develop cures for human diseases. ..
  5. RETINA: REVERSED POLARITY AND MORPHOGENESIS OF RPE
    ENRIQUE J RODRIGUEZ-BOULAN; Fiscal Year: 2013
    ..g. macular edema. ..
  6. Multifunctional roles for doublecortin (DCX)in neural development
    BETTINA R WINCKLER; Fiscal Year: 2013
    ..The objective of this proposal is to uncover the contributions of DCX-mediated endocytosis in neurodevelopment, including migration, axon growth and guidance and dendrite growth. ..
  7. The Plasma Membrane-Granule Interface in Exocytosis
    Ronald W Holz; Fiscal Year: 2011
    ..Aim 3 will build upon the same preliminary results motivating Aim 2 and will determine the relationship between curvature and the progression of protein interactions in compensatory, clathrin-mediated endocytosis. ..
  8. Clathrin adaptor function at the trans Golgi network and endosomes
    Gregory Payne; Fiscal Year: 2007
    ..Together these studies are expected to provide significant advances in our understanding of the fundamental process of ccv formation and protein sorting at the TGN and endosomes. ..
  9. CALCIUM IONS AND PRESYNAPTIC FUNCTION
    George Augustine; Fiscal Year: 2009
    ....
  10. Chemical inhibition of post Golgi traffic
    Mara Duncan; Fiscal Year: 2006
    ..Once identified, chemicals will be used to investigate the role of AP-1 in yeast and mammalian cells. ..
  11. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2007
    ..The new mutations that are found--and those that have already been found in preliminary efforts--will be isolated by positional cloning. ..
  12. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2006
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  13. Forward Genetic Analysis of the Innate Immune Contribution to MCMV Resistance
    Bruce Beutler; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  14. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2006
    ..In the case of mutations that abolish LPS tolerance, we will attempt to determine the net impact on host resistance to infection. ..
  15. TRAINING IN AGE-RELATED NEURODEGENERATIVE DISEASES
    Elliott Mufson; Fiscal Year: 2008
    ..Finally the program will provide a broad-base of knowledge on neurodegenerative disorders as well as other instruction important for enhancing the interpersonal and professional skills of our trainees. ..
  16. Molecular Mechanisms for IL-25-mediated Th2 Responses
    Xiaoxia Li; Fiscal Year: 2010
    ..With this improved understanding comes the potential to develop specific inhibitors of these pathways and perhaps novel therapeutics for the treatment of asthma. ..
  17. Remodeling of the M. tuberculosis cell wall during infection
    DAVID BRANCH MOODY; Fiscal Year: 2010
    ..Identification of the genes, enzymes and cell wall lipids that mediate adaptation to growth in tissues provides the information necessary to achieve this goal. ..
  18. Regulation of Type I Interferon Gene Expression in the Innate Immune Response
    Katherine A Fitzgerald; Fiscal Year: 2010
    ..abstract_text> ..
  19. SIGIRR A Negative Regulator of Toll-IL-IR Signaling
    Xiaoxia Li; Fiscal Year: 2009
    ..Specifically, the proposed studies should result in significant advances in the field of innate mucosal immunity and should also help us to determine the potential of SIGIRR as a target for developing anti-inflammatory drugs. ..
  20. Donor Antigen-Induced Peripheral Tolerance
    Dianne McKay; Fiscal Year: 2006
    ..We believe that intracellular signaling alterations that lead to alloantigen-induced tolerance may provide novel targets for a new generation of tolerizing immunosuppressive agents. ..
  21. Molecular Mechanisms of IL-1R-TLR-Mediated Signaling
    Xiaoxia Li; Fiscal Year: 2008
    ..The long-term objective is to develop more effective anti-inflammatory and anti-atherogenic small molecule drugs. [unreadable] [unreadable] [unreadable]..
  22. Herpes Simplex Virus Transmission Across Cell Junctions
    David Johnson; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  23. Phagocytosis of apoptotic cells: Signaling via GULP
    Kodi Ravichandran; Fiscal Year: 2007
    ..In these mouse studies, we will determine the effect on engulfment due to the absence of GULP, or disrupted GULP function, and any potential effects on autoimmunity due to defective engulfment. ..
  24. SCCOR in Translational Research in Acute Lung Injury
    Thomas Martin; Fiscal Year: 2007
    ..The proposed SCCOR Program will enhance understanding of the pathogenesis of lung injury and could lead to new treatments and improved long-term outcome for patients with acute lung injury. ..
  25. A novel method to discover genes that protect cells from alpha synuclein
    STEPHAN WITT; Fiscal Year: 2007
    ..This method allows us to screen libraries of genes- genes from any organism-to discover genes that protect against a-syn toxicity. [unreadable] [unreadable]..
  26. Cortactin in HNSSC tumor progression
    ALISSA WEAVER; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  27. HCMV US2 & US11 Inhibition of MHC Class II Presentation
    David Johnson; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  28. Ethnicity and the Diagnosis of Affective Illness
    Michael Escamilla; Fiscal Year: 2008
    ..The final objective is to determine whether Latinos are at risk for similar problems in diagnostic assessments and treatment assignment. ..
  29. EARLY ENDOTOXIN TOLERANCE: CELLULAR/MOLECULAR MECHANISMS
    Stefanie Vogel; Fiscal Year: 2004
    ..It is expected that, at the conclusion of this research, the mechanism of endotoxin tolerance and its potential impact on disease outcome in both sepsis and other diseases will be better understood. ..
  30. WILD DERIVED MOUSE STOCKS--NEW MODELS FOR AGING RESEARCH
    Richard Miller; Fiscal Year: 2004
    ....
  31. MECHANISMS OF DONOR SPLEEN INDUCED TRANSPLANT TOLERANCE
    Daniel Goldstein; Fiscal Year: 2004
    ..The career development program, mentor and didactic courses are designed to allow Dr. Goldstein to become an independent investigator by the end of the award period. ..
  32. GENETICS OF AGE SENSITIVE TRAITS IN MICE
    Richard Miller; Fiscal Year: 2003
    ..At best, the program may permit the localization of loci that influence multiple age-sensitive domains and are thus plausible candidates for genes that regulate the rate of aging per se. ..
  33. Novel whole-animal screens for anti-microbials
    FREDERICK AUSUBEL; Fiscal Year: 2009
    ..2) Develop a high throughput C. elegans - S. enterica curing assay. 3) Develop a high throughput screen for identifying MDR prump inhibitors in the C. elegans curing assays. ..
  34. MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW
    STEVEN GARLOW; Fiscal Year: 2004
    ..The circulating concentration of three hormones, cortisol, interleukin-1 and interleukin-6 will be measured before and after treatment, and correlated to platelet reactivity. ..
  35. Stress Resilience in an Animal Model of Depression
    Ruth Kohen; Fiscal Year: 2004
    ..If our hypothesis is true, it would mean a paradigm shift in our understanding of affective illness that could alter the focus of treatment from the current management of symptoms to their prevention ..
  36. ANALYSIS OF GOLGI MEMBRANE PROTEIN LOCALIZATION IN YEAST
    Steven Nothwehr; Fiscal Year: 2003
    ..Finally, several genes have been identified in genetic screens as defective in Golgi retention of proteins, and four of these will be investigated in further detail: grd20, grd21, grd22 and grd23. ..
  37. GENETIC ANALYSIS OF THE PLANT DEFENSE RESPONSE
    FREDERICK AUSUBEL; Fiscal Year: 2004
    ..elegans esp mutants. Finally, we propose to use genomic and reverse genetic approaches, including DNA microarray analysis, to identify C. elegans and Arabidopsis defense-related genes. ..
  38. Hantavirus Vaccines Based On Nonreplicating Adenoviruses
    David Johnson; Fiscal Year: 2005
    ..This will be a prelude to challenge experiments in which vaccinated hamsters will be challenged with Andes virus that causes a lethal pulmonary disease similar to that in humans. ..
  39. Gordon Conference on Neurotrophic Factors (2003,2005)
    Barbara Hempstead; Fiscal Year: 2005
    ..Hempstead and Y.-A. Barde) to profile new and young investigators as speakers in this Conference and for them to have a leadership role at this meeting. ..
  40. ROLES OF TOLL LIKE RECEPTORS IN INNATE IMMUNITY
    Stefanie Vogel; Fiscal Year: 2005
    ....
  41. MOLECULAR MECHANISMS OF LUNG INFLAMMATION
    Thomas Martin; Fiscal Year: 2002
    ....
  42. Molecular Mechanisms of MIG-10 function in axon guidance
    Christopher Quinn; Fiscal Year: 2005
    ..Information from this project will be beneficial in understanding disorders of the nervous system as well as the molecular basis of cancer. ..
  43. MICROTUBULE/KERATIN INTERACTIONS DURING SPERMATOGENESIS
    ABRAHAM KIERSZENBAUM; Fiscal Year: 2002
    ..Engineering mouse models in which the expression of K9 is null, is important for both reproductive biology and cancer research. ..
  44. Intracellular Signaling Triggered by Tall-1/BCMA
    Hong Bing Shu; Fiscal Year: 2005
    ..The genes and their protein products identified in this study may be used as molecular targets for drug development against certain immune-deficient and autoimmune diseases. ..
  45. NEUROTROPHINS AND CARDIOGENESIS
    Barbara Hempstead; Fiscal Year: 2002
    ....
  46. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2002
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  47. GENETICS OF SCHIZOPHRENIA IN LATINO POPULATIONS
    Michael Escamilla; Fiscal Year: 2003
    ....
  48. KINETICS AND MECHANISM OF THE HEAT SHOCK 70 PROTEIN DNAK
    STEPHAN WITT; Fiscal Year: 2002
    ..abstract_text> ..
  49. 5-HT2A RECEPTOR IN DEPRESSION: MOLECULAR MECHANISMS
    STEVEN GARLOW; Fiscal Year: 2003
    ..As the factors are characterized in the in vitro systems, their relevance to the regulation of the S-HT2A receptor in the brain will be tested in experimental animals. ..
  50. Act1 in CD40-/BAFFR-Mediated B Cell Survival
    Xiaoxia Li; Fiscal Year: 2009
    ..These findings will help us to elucidate the detailed regulatory mechanism for B cell homeostasis and opens new possibility to intervene the immune system. ..
  51. BDNF in depression, antidepressant action, and memory
    CRAIG POWELL; Fiscal Year: 2007
    ..We also propose to make use of focal injection of Cre-expressing AAV vectors into flox-BDNF mice to assess the specific brain subregions involved with greater temporal specificity. [unreadable] [unreadable]..
  52. Strategies to enhance immunity in aging
    Daniel Goldstein; Fiscal Year: 2007
    ..Goldstein to develop expertise in the biology of aging and how it relates to immunosenescence, ensuring that Dr. Goldstein will become a leading independent physician scientist in this area. [unreadable] [unreadable] [unreadable]..
  53. Innate immune responses in lymphatic filariasis
    AMY HISE; Fiscal Year: 2007
    ..abstract_text> ..
  54. Role of Innate Immunity in Transplantation Tolerance
    DANIEL ROBERT GOLDSTEIN; Fiscal Year: 2010
    ..g., MyD88 blockade at the time of tolerance induction). ..
  55. Mechanisms and Consequences of Toll Like Receptor Signal Transduction
    Stefanie Vogel; Fiscal Year: 2008
    ..3) Assess the mechanism of TLR tyrosine phosphorylation and its functional consequences. ..
  56. Genetics of Longevity and Age-Sensitive Traits in Mice
    Richard Miller; Fiscal Year: 2008
    ..abstract_text> ..
  57. Cortactin function in breast cancer metastasis
    ALISSA WEAVER; Fiscal Year: 2006
    ..We anticipate that these studies will yield important insight into the mechanisms by which metastasis occurs in vivo and potentially allow the identification of novel cytoskeleton-based targets for rational drug design. ..
  58. US Psychiatric Genetics Research Training Program
    Michael Escamilla; Fiscal Year: 2007
    ..Specific aims of the program follow. [unreadable] [unreadable]..
  59. Hypoxia and the Role of HIF-1 in the Ischemic Testis
    Michael Palladino; Fiscal Year: 2005
    ..abstract_text> ..