Paul Saftig

Summary

Affiliation: University of Kiel
Country: Germany

Publications

  1. ncbi Evaluation of the contribution of different ADAMs to tumor necrosis factor alpha (TNFalpha) shedding and of the function of the TNFalpha ectodomain in ensuring selective stimulated shedding by the TNFalpha convertase (TACE/ADAM17)
    Yufang Zheng
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 279:42898-906. 2004
  2. ncbi LAMP-2: a control step for phagosome and autophagosome maturation
    Paul Saftig
    Biochemical Institute, Christian Albrechts University Kiel, Kiel, Germany
    Autophagy 4:510-2. 2008
  3. pmc Natural history of alpha mannosidosis a longitudinal study
    Michael Beck
    Center for Pediatric and Adolescent Medicine, University Medical Center, Langenbeckstrase 1, 55131 Mainz, Germany
    Orphanet J Rare Dis 8:88. 2013
  4. pmc Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo
    Hermann C Altmeppen
    Institute of Neuropathology, University Medical Center Hamburg Eppendorf, D 20246 Hamburg, Germany
    Mol Neurodegener 6:36. 2011
  5. pmc Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
    Valerie Cullen
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Brain 2:5. 2009
  6. pmc Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits
    Stephanie Dauth
    School of Engineering and Science, Research Center MOLIFE Molecular Life Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    BMC Neurosci 12:74. 2011
  7. pmc Haematopoietic development and immunological function in the absence of cathepsin D
    Calogero Tulone
    Division of Infection and Immunity, UCL, London, UK
    BMC Immunol 8:22. 2007
  8. doi Lysosomal membrane proteins: life between acid and neutral conditions
    Paul Saftig
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Biochem Soc Trans 38:1420-3. 2010
  9. doi The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential?
    Paul Saftig
    Biochemical Institute, Christian Albrechts University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Eur J Cell Biol 90:527-35. 2011
  10. doi Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function
    Paul Saftig
    Department of Biochemistry, Christian Albrechts University, Kiel, Germany
    Nat Rev Mol Cell Biol 10:623-35. 2009

Detail Information

Publications79

  1. ncbi Evaluation of the contribution of different ADAMs to tumor necrosis factor alpha (TNFalpha) shedding and of the function of the TNFalpha ectodomain in ensuring selective stimulated shedding by the TNFalpha convertase (TACE/ADAM17)
    Yufang Zheng
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 279:42898-906. 2004
    ..Thus, selective stimulated processing of TNFalpha by ADAM17 in cells depends on the presence of an appropriate cleavage site as well as the inhibitory role of the TNF ectodomain toward other enzymes that can process this site...
  2. ncbi LAMP-2: a control step for phagosome and autophagosome maturation
    Paul Saftig
    Biochemical Institute, Christian Albrechts University Kiel, Kiel, Germany
    Autophagy 4:510-2. 2008
    ..Recent studies in LAMP double-knockout fibroblasts suggests that LAMP-deficiency impairs the dynein-mediated transport of lysosomes to perinuclear regions where fusion with (auto)phagosomes occurs...
  3. pmc Natural history of alpha mannosidosis a longitudinal study
    Michael Beck
    Center for Pediatric and Adolescent Medicine, University Medical Center, Langenbeckstrase 1, 55131 Mainz, Germany
    Orphanet J Rare Dis 8:88. 2013
    ..In addition, serum and urinary oligosaccharide levels were analysed...
  4. pmc Lack of a-disintegrin-and-metalloproteinase ADAM10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo
    Hermann C Altmeppen
    Institute of Neuropathology, University Medical Center Hamburg Eppendorf, D 20246 Hamburg, Germany
    Mol Neurodegener 6:36. 2011
    ..abstract:..
  5. pmc Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
    Valerie Cullen
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Mol Brain 2:5. 2009
    ..To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD), on aSyn processing...
  6. pmc Cathepsin K deficiency in mice induces structural and metabolic changes in the central nervous system that are associated with learning and memory deficits
    Stephanie Dauth
    School of Engineering and Science, Research Center MOLIFE Molecular Life Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    BMC Neurosci 12:74. 2011
    ..Cathepsin K has been recently detected in brain parenchyma and it has been linked to neurobehavioral disorders such as schizophrenia. Thus, the study of the functions that cathepsin K fulfils in the brain becomes highly relevant...
  7. pmc Haematopoietic development and immunological function in the absence of cathepsin D
    Calogero Tulone
    Division of Infection and Immunity, UCL, London, UK
    BMC Immunol 8:22. 2007
    ..This study examines the reconstitution and function of the immune system in the absence of cathepsin D, using bone marrow radiation chimaeras in which all haematopoietic cells are derived from cathepsin D deficient mice...
  8. doi Lysosomal membrane proteins: life between acid and neutral conditions
    Paul Saftig
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Biochem Soc Trans 38:1420-3. 2010
    ..Our recent investigations into the role of these proteins have not only increased our understanding of the endolysosomal system, but also supported their major role in cell physiology and the development of different diseases...
  9. doi The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential?
    Paul Saftig
    Biochemical Institute, Christian Albrechts University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Eur J Cell Biol 90:527-35. 2011
    ....
  10. doi Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function
    Paul Saftig
    Department of Biochemistry, Christian Albrechts University, Kiel, Germany
    Nat Rev Mol Cell Biol 10:623-35. 2009
    ....
  11. pmc ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation
    Thorsten Maretzky
    Biochemical Institute and Department of Dermatology, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    Proc Natl Acad Sci U S A 102:9182-7. 2005
    ..Our data strongly suggest that this protease constitutes a major regulatory element for the multiple functions of E-cadherin under physiological as well as pathological conditions...
  12. doi A critical histidine residue within LIMP-2 mediates pH sensitive binding to its ligand β-glucocerebrosidase
    Christina Zachos
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098, Kiel, Germany
    Traffic 13:1113-23. 2012
    ..This residue is in close proximity to a proposed coiled-coil domain, which determines the binding to GC and may function as a critical pH sensor...
  13. doi Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10
    Johannes Prox
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, 24098, Kiel, Germany
    Cell Mol Life Sci 69:2919-32. 2012
    ..Therapeutic manipulation of its expression levels may be an additional approach to specifically regulate the activity of the amyloid precursor protein alpha-secretase ADAM10...
  14. ncbi Regulated ADAM10-dependent ectodomain shedding of gamma-protocadherin C3 modulates cell-cell adhesion
    Karina Reiss
    Biochemical Institute, Christian Albrecht University Kiel, D 24098 Kiel, Germany
    J Biol Chem 281:21735-44. 2006
    ..The identification of ADAM10 as the protease responsible for constitutive and regulated Pcdh gamma shedding may therefore provide new insight into the regulation of Pcdh gamma functions...
  15. ncbi Regulated shedding of transmembrane chemokines by the disintegrin and metalloproteinase 10 facilitates detachment of adherent leukocytes
    Christian Hundhausen
    Institute of Biochemistry, Christian Albrechts University, Kiel, Germany
    J Immunol 178:8064-72. 2007
    ..These data provide evidence for an inducible release mechanism via ADAM10 potentially important for leukocyte diapedesis...
  16. pmc ADAM10 regulates endothelial permeability and T-Cell transmigration by proteolysis of vascular endothelial cadherin
    Beate Schulz
    Biochemical Institute, Christian Albrecht University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Circ Res 102:1192-201. 2008
    ....
  17. doi ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis
    Thorsten Maretzky
    Biochemical Institute, Christian Albrecht University Kiel, Kiel, Germany
    J Invest Dermatol 128:1737-46. 2008
    ....
  18. pmc L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth
    Thorsten Maretzky
    Biochemical Institute, Christian Albrechts University Kiel, Germany
    Mol Cell Biol 25:9040-53. 2005
    ..Thus, our data identify ADAM10 and ADAM17 as differentially regulated L1 membrane sheddases, both critically affecting the physiological functions of this adhesion protein...
  19. doi Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail
    Jörg Behnke
    Biochemical Institute, Christian Albrechts University Kiel, Kiel, Germany
    FEBS Lett 585:2951-7. 2011
    ..This motif accounts for the differential localisation of the homologous proteases SPPL2a and SPPL2b and thereby influences the access to substrates and biological function of SPPL2a...
  20. ncbi The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10
    Soeren Abel
    Institute for Biochemistry, Christian Albrechts University, Kiel, Germany
    J Immunol 172:6362-72. 2004
    ..Hence, during inflammation in the vasculature, ADAM10 may act as a CXCL16 sheddase and thereby finely control the expression and function of CXCL16 in the inflamed tissue...
  21. pmc ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling
    Karina Reiss
    Biochemical Institute, Christian Albrechts University Kiel, Kiel, Germany
    EMBO J 24:742-52. 2005
    ....
  22. ncbi Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE)
    Vance Matthews
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Germany
    J Biol Chem 278:38829-39. 2003
    ..For decades, high cholesterol levels have been considered harmful. This study indicates that low cholesterol levels may play a role in shedding of the membrane-bound IL-6R and thereby in the immunopathogenesis of human diseases...
  23. doi Disease-causing mutations within the lysosomal integral membrane protein type 2 (LIMP-2) reveal the nature of binding to its ligand beta-glucocerebrosidase
    Judith Blanz
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Hum Mol Genet 19:563-72. 2010
    ....
  24. doi Molecular characterisation of 'transmembrane protein 192' (TMEM192), a novel protein of the lysosomal membrane
    Bernd Schröder
    Biochemical Institute, Christian Albrechts University, D 24118 Kiel, Germany
    Biol Chem 391:695-704. 2010
    ..TMEM192 was found to be strongly expressed in human kidney, liver, lung and pancreas tissue. The widespread tissue distribution could suggest an important role of TMEM192 for lysosomal function...
  25. doi Role for LAMP-2 in endosomal cholesterol transport
    Alexander Schneede
    Institute of Biochemistry, University of Kiel, Kiel, Germany
    J Cell Mol Med 15:280-95. 2011
    ..Taken together, our results suggest that LAMP-2, its luminal domain in particular, plays a critical role in endosomal cholesterol transport and that this is distinct from the chaperone-mediated autophagy function of LAMP-2...
  26. ncbi Structural determinants of M-type KCNQ (Kv7) K+ channel assembly
    Michael Schwake
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, D 24098 Kiel, Germany
    J Neurosci 26:3757-66. 2006
    ....
  27. ncbi Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM10 and SPPL2a/SPPL2b
    Lucas Martin
    Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 283:1644-52. 2008
    ....
  28. ncbi Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme
    Gil G Westmeyer
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 279:53205-12. 2004
    ..Dimerization of BACE might, thus, facilitate binding and cleavage of physiological substrates...
  29. doi Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions
    Johannes Prox
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, D 24098 Kiel, Germany
    J Neurosci 33:12915-28, 12928a. 2013
    ..Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain. ..
  30. doi Disrupted in renal carcinoma 2 (DIRC2), a novel transporter of the lysosomal membrane, is proteolytically processed by cathepsin L
    Lalu Rudyat Telly Savalas
    Biochemical Institute, Christian Albrechts University, Kiel, Germany
    Biochem J 439:113-28. 2011
    ..Taken together, these data strongly support the idea that DIRC2 is an electrogenic lysosomal metabolite transporter which is subjected to and presumably modulated by limited proteolytic processing...
  31. ncbi Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal-associated membrane protein-2 knockout mice
    Wouter Beertsen
    Biochemical Institute, Christian Albrechts University Kiel, and Institute of Infection Medicine, University Hospital Schleswig Holstein, Germany
    J Immunol 180:475-82. 2008
    ..It also underscores the requirement of lysosomal fusion events to provide sufficient antimicrobial activity in PMNs, which is needed to prevent periodontal disease...
  32. pmc The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain
    Janna Schneppenheim
    Biochemical Institute, Christian Albrechts University of Kiel, D 24118 Kiel, Germany
    J Exp Med 210:41-58. 2013
    ....
  33. pmc Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
    Athena Chalaris
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Exp Med 207:1617-24. 2010
    ..Thus, our mouse model will help investigate ADAM17 as a potential drug target...
  34. ncbi Control of peripheral nerve myelination by the beta-secretase BACE1
    Michael Willem
    Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Schillerstrasse 44, Ludwig Maximilians University, 80336 Munich, Germany
    Science 314:664-6. 2006
    ..Thus, BACE1 is required for myelination and correct bundling of axons by Schwann cells, probably through processing of type III NRG1...
  35. pmc Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts
    Eeva Liisa Eskelinen
    Institute of Biochemistry, University of Kiel, D 24098 Kiel, Germany
    Mol Biol Cell 15:3132-45. 2004
    ..Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis...
  36. pmc The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling
    Silvio Weber
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, Kiel, Germany
    Development 138:495-505. 2011
    ..The data identify Adam10 as the major Site-2 processing enzyme for Notch in the epidermis in vivo, and thus as a central regulator of skin development and maintenance...
  37. doi Two dileucine motifs mediate late endosomal/lysosomal targeting of transmembrane protein 192 (TMEM192) and a C-terminal cysteine residue is responsible for disulfide bond formation in TMEM192 homodimers
    Jörg Behnke
    Biochemical Institute, Christian Albrechts University Kiel, Otto Hahn Platz 9, 24118 Kiel, Germany
    Biochem J 434:219-31. 2011
    ..These findings may imply close proximity of the C-termini in TMEM192 dimers and a possible involvement of this part of the protein in dimer assembly...
  38. doi Lysosomal membrane proteins and their central role in physiology
    Michael Schwake
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098, Kiel, Germany
    Traffic 14:739-48. 2013
    ..We are only beginning to understand the complex composition and function of these proteins which are tightly linked to processes occurring throughout the endocytic and biosynthetic pathways...
  39. ncbi Self-assembly of the isolated KCNQ2 subunit interaction domain
    Christina Wehling
    Institute of Biochemistry, Christian Albrechts University Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    FEBS Lett 581:1594-8. 2007
    ..Whereas structural integrity of the second coiled-coil motif is crucial for tetramer formation, that of the first motif is less important. These data suggest a crucial role of coiled-coil motifs in tetrameric KCNQ channel assembly...
  40. ncbi Mannose 6-phosphate receptors, Niemann-Pick C2 protein, and lysosomal cholesterol accumulation
    Marion Willenborg
    Institute of Biochemistry, University of Kiel, D 24098 Kiel, Germany
    J Lipid Res 46:2559-69. 2005
    ..In addition, we observed an upregulation of NPC1 protein and mRNA in the MPR-double-deficient cells. Taken together, our results suggest that the lysosomal targeting of NPC2 is strictly dependent on MPRs in fibroblasts...
  41. pmc Mannose 6 dephosphorylation of lysosomal proteins mediated by acid phosphatases Acp2 and Acp5
    Georgia Makrypidi
    Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Mol Cell Biol 32:774-82. 2012
    ..The data demonstrate that dephosphorylation of Man6P-containing lysosomal proteins requires the concerted action of Acp2 and Acp5 and is needed for hydrolysis and removal of degradation products...
  42. ncbi Role for Rab7 in maturation of late autophagic vacuoles
    Stefanie Jäger
    Institute of Biochemistry, University of Kiel, Olshausenstr 40, 24098 Kiel, Germany
    J Cell Sci 117:4837-48. 2004
    ..In conclusion, our results showed a role for Rab7 in the final maturation of late autophagic vacuoles...
  43. doi Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice
    Judith Blanz
    Biochemical Institute, University of Kiel, Kiel, Germany
    Hum Mol Genet 17:3437-45. 2008
    ..These data suggest that high-dose injections of low phosphorylated enzymes might be an interesting option to efficiently treat LSDs with CNS involvement...
  44. pmc Deafness in LIMP2-deficient mice due to early loss of the potassium channel KCNQ1/KCNE1 in marginal cells of the stria vascularis
    Marlies Knipper
    Biochemical Institute, Christian Albrechts University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Physiol 576:73-86. 2006
    ..Our findings suggest an important role for LIMP2 in the control of the localization and the level of apically expressed membrane proteins such as KCNQ1, KCNE1 and megalin in the stria vascularis...
  45. ncbi Breaking up the tie: disintegrin-like metalloproteinases as regulators of cell migration in inflammation and invasion
    Karina Reiss
    Biochemical Institute, Christian Albrecht University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Pharmacol Ther 111:985-1006. 2006
    ..Moreover, metalloproteases of the ADAM family are emerging as promising targets for new therapeutic options...
  46. doi Regulation of adult hematopoiesis by the a disintegrin and metalloproteinase 10 (ADAM10)
    Silvio Weber
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstrasse 40, D 24098 Kiel, Germany
    Biochem Biophys Res Commun 442:234-41. 2013
    ..Our findings indicate that a tightly controlled ADAM10 expression is needed to balance hematopoietic cell-fate decisions in adult mice. ..
  47. ncbi At the acidic edge: emerging functions for lysosomal membrane proteins
    Eeva Liisa Eskelinen
    Department of Biochemistry, University of Kiel, Eduard Buchner Haus, Olshausenstrasse 40, D 24098 Kiel, Germany
    Trends Cell Biol 13:137-45. 2003
    ..The pivotal function of lysosomal membrane proteins is also highlighted by the recent identification of disease-causing mutations in cystine and sialic acid transporter proteins, leading to nephropathic cystinosis and Salla disease...
  48. ncbi Unifying nomenclature for the isoforms of the lysosomal membrane protein LAMP-2
    Eeva Liisa Eskelinen
    University of Kiel, Institute of Biochemistry, Kiel, Germany
    Traffic 6:1058-61. 2005
    ..To avoid confusion in the literature, we further propose to adopt the use of capital letters for the updated nomenclature of all the isoforms in all three species: LAMP-2A, LAMP-2B, and LAMP-2C...
  49. doi The "a disintegrin and metalloprotease" (ADAM) family of sheddases: physiological and cellular functions
    Karina Reiss
    Biochemical Institute, Christian Albrecht University Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    Semin Cell Dev Biol 20:126-37. 2009
    ..ADAMs usually trigger the first step in regulated intramembrane proteolysis leading to activation of intracellular signalling pathways and the release of functional soluble ectodomains...
  50. doi Physiological functions of the amyloid precursor protein secretases ADAM10, BACE1, and presenilin
    Johannes Prox
    Biochemical Institute, Christian Albrechts University Kiel, Olshausenstr 40, 24098 Kiel, Germany
    Exp Brain Res 217:331-41. 2012
    ..This review attempts to summarize selected aspects of the current view of the multiple roles such proteases play in health and disease...
  51. doi Molecular insights into mechanisms of intramembrane proteolysis through signal peptide peptidase (SPP)
    Bernd Schröder
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Germany
    Biochem J 427:e1-3. 2010
    ..These large oligomeric membrane protein aggregates may then be degraded by the proteasome or autophagy...
  52. ncbi Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine
    Anne Schenzer
    Institute of Biochemistry, Christian Albrechts University Kiel, D 24098 Kiel, Germany
    J Neurosci 25:5051-60. 2005
    ..Transfer of the tryptophan into the KCNQ1 scaffold resulted in retigabine-sensitive heteromers, suggesting that the tryptophan is necessary in all KCNQ subunits forming a functional tetramer to confer drug sensitivity...
  53. doi The proteome of lysosomes
    Bernd A Schröder
    Biochemical Institute, Christian Albrechts University, Kiel, Germany
    Proteomics 10:4053-76. 2010
    ....
  54. ncbi The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion
    Christian Hundhausen
    Institute for Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 102:1186-95. 2003
    ..Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers...
  55. ncbi beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase
    Hon Kit Wong
    Laboratories for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan
    J Biol Chem 280:23009-17. 2005
    ..These results may provide new insights into the underlying pathology of Alzheimer disease...
  56. ncbi A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology
    Toshio Kuronita
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3 1 1, Fukuoka 812 8582, Japan
    J Cell Sci 115:4117-31. 2002
    ..Thus, these findings provide important new insights into the role of LGP85 in the biogenesis and the maintenance of endosomes/lysosomes. We conclude that LGP85 may participate in reorganizing the endosomal/lysosomal compartments...
  57. ncbi Natural soluble interleukin-15Ralpha is generated by cleavage that involves the tumor necrosis factor-alpha-converting enzyme (TACE/ADAM17)
    Vadim Budagian
    Center for Cancer Drug Discovery and Development, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:40368-75. 2004
    ..The existence of natural sIL-15Ralpha offers novel insights into the complex biology of IL-15 and envisages a new level for therapeutic intervention...
  58. ncbi Evidence for a critical role of the tumor necrosis factor alpha convertase (TACE) in ectodomain shedding of the p75 neurotrophin receptor (p75NTR)
    Gisela Weskamp
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 279:4241-9. 2004
    ..Because ectodomain shedding of p75NTR releases a soluble ectodomain and could also be a prerequisite for its regulated intramembrane proteolysis, these findings may have important implications for the functional regulation of p75NTR...
  59. ncbi Deficiency of mannose 6-phosphate receptors and lysosomal storage: a morphometric analysis of hepatocytes of neonatal mice
    Jacques P M Schellens
    Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, P O Box 22700, 1100 DE, Amsterdam, The Netherlands
    Cell Biol Int 27:897-902. 2003
    ..It is concluded that in hepatocytes of MPR-deficient neonatal mice lysosomal storage occurs when both MPRs are lacking, whereas deficiency of CI-MPR only has no effect on the ultrastructure of the lysosomal system...
  60. ncbi LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice
    Alexander Christian Gamp
    Zentrum Biochemie und Molekulare Zellbiologie, Abt Biochemie II, Universitat Gottingen, 37073 Gottingen, Germany
    Hum Mol Genet 12:631-46. 2003
    ..The phenotype of LIMP-2-deficient mice stimulates the search for mutations in human disorders associated with degeneration of the stria vascularis and/or demyelinization of peripheral nerves...
  61. pmc Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx
    Keisuke Horiuchi
    Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA
    Mol Biol Cell 18:176-88. 2007
    ....
  62. pmc Role of LAMP-2 in lysosome biogenesis and autophagy
    Eeva Liisa Eskelinen
    Centre for High Resolution Imaging and Processing, School of Life Sciences, University of Dundee, Scotland, UK
    Mol Biol Cell 13:3355-68. 2002
    ..Autophagic vacuoles may accumulate due to impaired capacity for lysosomal degradation...
  63. pmc Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
    Umut Sahin
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Box 368, 1275 York Avenue, New York, NY 10021, USA
    J Cell Biol 164:769-79. 2004
    ..Identification of EGFR ligand sheddases is a crucial step toward understanding the mechanism underlying ectodomain release, and has implications for designing novel inhibitors of EGFR-dependent tumors...
  64. pmc Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
    Cary Esselens
    Membrane Trafficking Laboratory, CME VIB04, Gasthuisberg KU Leuven, 3000 Leuven, Belgium
    J Cell Biol 166:1041-54. 2004
    ..Collectively, PS1 deficiency affects in a gamma-secretase-independent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes...
  65. ncbi Decreased intracellular degradation of insulin-like growth factor binding protein-3 in cathepsin L-deficient fibroblasts
    Olaf Zwad
    Cildren s Hospital Biochemistry, University of Hamburg, Germany
    FEBS Lett 510:211-5. 2002
    ..This suggests the involvement of CTSL in the intracellular degradation of IGFBP-3 representing a new mechanism to regulate the extracellular concentration of IGFBP-3...
  66. ncbi Arrested maturation of Neisseria-containing phagosomes in the absence of the lysosome-associated membrane proteins, LAMP-1 and LAMP-2
    Marcelo G Binker
    Cell Biology Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada
    Cell Microbiol 9:2153-66. 2007
    ....
  67. pmc LAMP proteins are required for fusion of lysosomes with phagosomes
    Kassidy K Huynh
    Division of Cell Biology, The Hospital for Sick Children, Toronto, Canada
    EMBO J 26:313-24. 2007
    ..Time-lapse cinematography revealed that late endosomes/lysosomes as well as phagosomes lacking LAMP-1 and LAMP-2 had reduced ability to move toward the microtubule-organizing center, likely precluding their interaction with each other...
  68. ncbi Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice
    Ryo Yamasaki
    Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka 812 8582, Japan
    Mol Cell Neurosci 35:573-84. 2007
    ..The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO...
  69. ncbi LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase
    David Reczek
    Genzyme Corporation, 1 Mountain Road, Framingham, MA 01701, USA
    Cell 131:770-83. 2007
    ..These data support a role for LIMP-2 as the mannose-6-phosphate-independent trafficking receptor for beta-glucocerebrosidase...
  70. pmc Proteomic identification of desmoglein 2 and activated leukocyte cell adhesion molecule as substrates of ADAM17 and ADAM10 by difference gel electrophoresis
    Joan J Bech-Serra
    Medical Oncology Research Program, Vall d Hebron University Hospital Research Institute, 08035 Barcelona, Spain
    Mol Cell Biol 26:5086-95. 2006
    ..Since loss of cell adhesion is an early event in tumor development, these results suggest that ADAM17 is a useful target in anticancer therapy...
  71. ncbi Cutting edge: a novel nonoxidative phagosomal mechanism exerted by cathepsin-D controls Listeria monocytogenes intracellular growth
    Elida Del Cerro-Vadillo
    Servicio de Inmunologia, Hospital Universitario Marques de Valdecilla, Servicio Cantabro de Salud, Santander, Spain
    J Immunol 176:1321-5. 2006
    ..Based on infection experiments with mutant bacteria, in vitro degradation, and immunoprecipitation experiments, we suggest that a major target of cathepsin D is the main virulence factor listeriolysin O...
  72. ncbi Cathepsin D deficiency induces persistent neurodegeneration in the absence of Bax-dependent apoptosis
    John J Shacka
    Department of Pathology, Neuropathology Division, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    J Neurosci 27:2081-90. 2007
    ....
  73. pmc Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease)
    Masato Koike
    Department of Cell Biology and Neurosciences, Osaka University Graduate School of Medicine, Suita, Japan
    Am J Pathol 167:1713-28. 2005
    ..These data strongly argue for a major involvement of autophagy in the pathogenesis of Batten disease/lysosomal storage disorders...
  74. doi Lysosomal myopathies: an excessive build-up in autophagosomes is too much to handle
    May Christine Malicdan
    Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187 8502, Japan
    Neuromuscul Disord 18:521-9. 2008
    ..In this review, these disorders are briefly characterized, and the role of autophagy in the context of the pathomechanism of these disorders is highlighted...
  75. doi Live longer with LAMP-2
    Paul Saftig
    Nat Med 14:909-10. 2008
  76. ncbi The NH(2)-terminal transmembrane and lumenal domains of LGP85 are needed for the formation of enlarged endosomes/lysosomes
    Toshio Kuronita
    Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3 1 1 Maidashi, Fukuoka 812 8582, Japan
    Traffic 6:895-906. 2005
    ..Taken together, these results indicate the involvement of distinct domain of LGP85 in the targeting to, and biogenesis and maintenance of, ELC...
  77. ncbi Neurocognitive and psychotiform behavioral alterations and enhanced hippocampal long-term potentiation in transgenic mice displaying neuropathological features of human alpha-mannosidosis
    Rudi D'Hooge
    Laboratory of Biological Psychology, University of Leuven, B 3000 Leuven, Belgium
    J Neurosci 25:6539-49. 2005
    ..We propose that prominent storage and enhanced LTP in hippocampus have contributed to these specific behavioral alterations in alpha-mannosidase-deficient mice...
  78. ncbi The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death
    Rosa Ana Gonzalez-Polo
    CNRS UMR8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    J Cell Sci 118:3091-102. 2005
    ..Altogether, these data indicate that accumulation of autophagic vacuoles can precede apoptotic cell death. These findings argue against the clear-cut distinction between type 1 (apoptotic) and type 2 (autophagic) cell death...
  79. ncbi Altered regulation of phosphatidylinositol 3-kinase signaling in cathepsin D-deficient brain
    Ken C Walls
    Department of Cell Biology, Neuropathology Division, University of Alabama at Birmingham, Birmingham Alabama 35294 0017, USA
    Autophagy 3:222-9. 2007
    ..Together these observations indicate a pronounced decrease in pro-survival PI3-K signaling in CD-/- brain that may contribute to autophagic stress-induced and apoptotic neuropathology...