Ramanujan S Hegde

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Signal sequence insufficiency contributes to neurodegeneration caused by transmembrane prion protein
    Neena S Rane
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 188:515-26. 2010
  2. pmc Protein targeting and degradation are coupled for elimination of mislocalized proteins
    Tara Hessa
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 475:394-7. 2011
  3. pmc Compartment-restricted biotinylation reveals novel features of prion protein metabolism in vivo
    Amy B Emerman
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 21:4325-37. 2010
  4. pmc A ribosome-associating factor chaperones tail-anchored membrane proteins
    Malaiyalam Mariappan
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 466:1120-4. 2010
  5. pmc Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane
    Ryen D Fons
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 160:529-39. 2003
  6. pmc Selective processing and metabolism of disease-causing mutant prion proteins
    Aarthi Ashok
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 5:e1000479. 2009
  7. pmc The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells
    Erik L Snapp
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Dr, Bldg 18, Rm 101, Bethesda, MD 20892, USA
    J Cell Biol 164:997-1007. 2004
  8. pmc The concept of translocational regulation
    Ramanujan S Hegde
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 182:225-32. 2008
  9. ncbi request reprint Prion protein trafficking and the development of neurodegeneration
    Ramanujan S Hegde
    Cell Biology and Metabolism Branch, NICHD National Institutes of Health, Bethesda, MD 20892, USA
    Trends Neurosci 26:337-9. 2003
  10. pmc Quality and quantity control at the endoplasmic reticulum
    Ramanujan S Hegde
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Curr Opin Cell Biol 22:437-46. 2010

Collaborators

Detail Information

Publications47

  1. pmc Signal sequence insufficiency contributes to neurodegeneration caused by transmembrane prion protein
    Neena S Rane
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 188:515-26. 2010
    ..Thus, signal sequences are functionally nonequivalent in vivo, with intrinsic inefficiency of the native PrP signal being required for pathogenesis of a subset of disease-causing PrP mutations...
  2. pmc Protein targeting and degradation are coupled for elimination of mislocalized proteins
    Tara Hessa
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 475:394-7. 2011
    ..We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery...
  3. pmc Compartment-restricted biotinylation reveals novel features of prion protein metabolism in vivo
    Amy B Emerman
    Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 21:4325-37. 2010
    ..Thus, spatiotemporal tagging has uncovered novel aspects of normal and mutant PrP metabolism and should be readily applicable to the analysis of minor topologic isoforms of other proteins...
  4. pmc A ribosome-associating factor chaperones tail-anchored membrane proteins
    Malaiyalam Mariappan
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 466:1120-4. 2010
    ..Thus, the Bat3 complex acts as a TMD-selective chaperone that effectively channels TA proteins to the TRC40 insertion pathway...
  5. pmc Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane
    Ryen D Fons
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 160:529-39. 2003
    ..These results identify the TRAP complex as a functional component of the translocon and demonstrate that it acts in a substrate-specific manner to facilitate the initiation of protein translocation...
  6. pmc Selective processing and metabolism of disease-causing mutant prion proteins
    Aarthi Ashok
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 5:e1000479. 2009
    ....
  7. pmc The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells
    Erik L Snapp
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Dr, Bldg 18, Rm 101, Bethesda, MD 20892, USA
    J Cell Biol 164:997-1007. 2004
    ....
  8. pmc The concept of translocational regulation
    Ramanujan S Hegde
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 182:225-32. 2008
    ..A conceptual framework for translocational regulation is proposed based on our current mechanistic understanding of ER protein translocation and general principles of regulatory control...
  9. ncbi request reprint Prion protein trafficking and the development of neurodegeneration
    Ramanujan S Hegde
    Cell Biology and Metabolism Branch, NICHD National Institutes of Health, Bethesda, MD 20892, USA
    Trends Neurosci 26:337-9. 2003
    ..Recent studies examining the occurrence and consequences of inappropriate cytoplasmic expression of the normally cell-surface PrP underscore an emerging role for PrP trafficking in prion disease pathogenesis...
  10. pmc Quality and quantity control at the endoplasmic reticulum
    Ramanujan S Hegde
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Curr Opin Cell Biol 22:437-46. 2010
    ..Here, we synthesize current concepts underlying the pathways that mediate protein degradation from the ER and their deployment under physiologic and pathologic conditions...
  11. ncbi request reprint The surprising complexity of signal sequences
    Ramanujan S Hegde
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Biochem Sci 31:563-71. 2006
    ....
  12. pmc The efficiency of protein compartmentalization into the secretory pathway
    Corinna G Levine
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 16:279-91. 2005
    ..These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins...
  13. pmc Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway
    Sang Wook Kang
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Drive, Building 18T, Room 101, Bethesda, MD 20892, USA
    Cell 127:999-1013. 2006
    ..Conversely, pharmacologically augmenting pQC during ER stress proved protective. Thus, protein translocation is a physiologically regulated process that is utilized for pQC as part of the ER stress response...
  14. pmc Reduced translocation of nascent prion protein during ER stress contributes to neurodegeneration
    Neena S Rane
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 15:359-70. 2008
    ..We propose that one mechanism of prion-mediated neurodegeneration involves an indirect ER stress-dependent effect on nascent PrP biosynthesis and metabolism...
  15. pmc Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins
    Oishee Chakrabarti
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 22:1625-37. 2011
    ....
  16. pmc Relocalization of STIM1 for activation of store-operated Ca(2+) entry is determined by the depletion of subplasma membrane endoplasmic reticulum Ca(2+) store
    Hwei Ling Ong
    Secretory Physiology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 282:12176-85. 2007
    ..Thus, the mechanism involved in regulation of SOCE is contained within the ER-plasma membrane junctional region...
  17. pmc Prion protein biosynthesis and its emerging role in neurodegeneration
    Oishee Chakrabarti
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Biochem Sci 34:287-95. 2009
    ..Indeed, our current understanding of normal PrP cell biology, coupled with a growing appreciation of its complex metabolism, is providing new hypotheses for PrP-mediated neurodegeneration...
  18. pmc Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cells
    Erik L Snapp
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Drive, Building 18, Room 101, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:6536-41. 2006
    ..Our findings provide insight into the normal organization and dynamics of an ER chaperone and characterize the capacity of the ER to maintain homeostasis during acute changes in chaperone activity and availability...
  19. ncbi request reprint Identification of a targeting factor for posttranslational membrane protein insertion into the ER
    Sandra Stefanovic
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 128:1147-59. 2007
    ..Thus, TRC40/Asna-1 represents an integral component of a posttranslational pathway of membrane protein insertion whose targeting is mediated by TRC...
  20. pmc Protection from cytosolic prion protein toxicity by modulation of protein translocation
    Neena S Rane
    Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, MD 20892 5430, USA
    EMBO J 23:4550-9. 2004
    ..These results suggest that a substantial proportion of the cell's constitutive proteasomal burden may consist of proteins that, like PrP, fail to cotranslationally enter the secretory pathway with high fidelity...
  21. pmc Retrotranslocation of prion proteins from the endoplasmic reticulum by preventing GPI signal transamidation
    Aarthi Ashok
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Biol Cell 19:3463-76. 2008
    ..As each GPI signal sequence is unique, these results also identify signal recognition by the GPI-transamidase as a potential step for selective small molecule perturbation of PrP expression...
  22. ncbi request reprint Intracellular Ca(2+) release via the ER translocon activates store-operated calcium entry
    Hwei L Ong
    Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA
    Pflugers Arch 453:797-808. 2007
    ..We suggest that the functional coupling between SOCE and protein synthesis is likely to be critical for maintaining [Ca(2+)](ER) within a range that is required to prevent ER stress during changes in cellular translational activity...
  23. pmc Formation of stacked ER cisternae by low affinity protein interactions
    Erik L Snapp
    Cell Biology and Metabolism Branch, National Institutes of Child Health and Human Development, National Institutes of Health, 18 Library Dr, Bldg 18T, Rm 101, Bethesda, MD 20892, USA
    J Cell Biol 163:257-69. 2003
    ..This mechanism may underlie the formation of other stacked membrane structures within cells...
  24. pmc A calmodulin-dependent translocation pathway for small secretory proteins
    Sichen Shao
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 147:1576-88. 2011
    ..These findings establish a mammalian posttranslational pathway for small-protein secretion and identify an unexpected role for calmodulin in chaperoning these precursors safely through the cytosol...
  25. pmc The mechanism of membrane-associated steps in tail-anchored protein insertion
    Malaiyalam Mariappan
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 477:61-6. 2011
    ..After releasing its TA protein cargo, the now-vacant Get3 recycles back to the cytosol concomitant with ATP binding. This work provides a detailed structural and mechanistic framework for the minimal TA protein insertion cycle...
  26. pmc Cotranslational partitioning of nascent prion protein into multiple populations at the translocation channel
    Soo Jung Kim
    Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Biol Cell 13:3775-86. 2002
    ....
  27. ncbi request reprint Regulation of protein compartmentalization expands the diversity of protein function
    Kelly L Shaffer
    Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    Dev Cell 9:545-54. 2005
    ..We propose that regulation of protein translocation represents a potentially general mechanism for generating diversity of protein function...
  28. doi request reprint Membrane protein insertion at the endoplasmic reticulum
    Sichen Shao
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA
    Annu Rev Cell Dev Biol 27:25-56. 2011
    ..Here, we review the conceptual and mechanistic themes underlying these core membrane protein insertion pathways, the complexities that challenge our understanding, and future directions to overcome these obstacles...
  29. ncbi request reprint Signal sequences control gating of the protein translocation channel in a substrate-specific manner
    Soo Jung Kim
    Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892, USA
    Dev Cell 2:207-17. 2002
    ....
  30. pmc In vitro dissection of protein translocation into the mammalian endoplasmic reticulum
    Ajay Sharma
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 619:339-63. 2010
    ..Variations of these methods should be applicable not only to forward protein translocation systems but also for dissecting other poorly understood membrane-associated processes such as retrotranslocation...
  31. pmc Deubiquitinases sharpen substrate discrimination during membrane protein degradation from the ER
    Zai Rong Zhang
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Drive, Bethesda, MD 20892, USA
    Cell 154:609-22. 2013
    ..These results provide a conceptual framework for substrate discrimination during membrane protein quality control. ..
  32. pmc Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegeneration
    Oishee Chakrabarti
    Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
    Cell 137:1136-47. 2009
    ..Thus, transient or partial exposure of PrP to the cytosol leads to inappropriate Mgrn sequestration that contributes to neuronal dysfunction and disease...
  33. ncbi request reprint Targeting and beyond: new roles for old signal sequences
    Ramanujan S Hegde
    Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell 10:697-8. 2002
    ..Recent work is beginning to shed light on some of the ways the cell decodes and exploits additional functions encoded within signal sequences...
  34. doi request reprint Histone deacetylase inhibitors influence chemotherapy transport by modulating expression and trafficking of a common polymorphic variant of the ABCG2 efflux transporter
    Agnes Basseville
    Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 72:3642-51. 2012
    ..Together, these results showed how HDIs are able to restore wild-type functions of the common Q141K polymorphic isoform of ABCG2. More broadly, our findings expand the potential uses of HDIs in the clinic...
  35. pmc Prions and retroviruses: an endosomal rendezvous?
    Aarthi Ashok
    Cell Biology and Metabolism Branch of the National Institute of Child Health and Human Development, National Institutes of Health, 18 Library Drive, Building 18, Room 101, Bethesda, MD 20892, USA
    EMBO Rep 7:685-7. 2006
  36. pmc Lighting up the stressed ER
    Sang Wook Kang
    National Institutes of Health, Bethesda, MD 20892, USA
    Cell 135:787-9. 2008
    ..In this issue, Merksamer et al. (2008) exploit a redox-sensitive fluorescent protein to monitor the environment inside the ER of living yeast, illuminating how this organelle responds to different perturbations...
  37. doi request reprint Arginine 383 is a crucial residue in ABCG2 biogenesis
    Orsolya Polgar
    Medical Oncology Branch, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA
    Biochim Biophys Acta 1788:1434-43. 2009
    ..In conclusion, arginine 383 is a crucial residue for ABCG2 biogenesis, where even the most conservative mutations have a large impact...
  38. ncbi request reprint ER Stress-Induced Clearance of Misfolded GPI-Anchored Proteins via the Secretory Pathway
    Prasanna Satpute-Krishnan
    Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
    Cell 158:522-33. 2014
    ..Thus, this rapid response alleviates the elevated burden of misfolded proteins in the ER at the onset of ER stress, promoting protein homeostasis in the ER. ..
  39. ncbi request reprint A substrate-specific inhibitor of protein translocation into the endoplasmic reticulum
    Jennifer L Garrison
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94107, USA
    Nature 436:285-9. 2005
    ..Thus, the range of substrates accommodated by the channel can be specifically and reversibly modulated by a cell-permeable small molecule that alters the interaction between signal sequences and the Sec61 complex...
  40. pmc Transmembrane topogenesis of a tail-anchored protein is modulated by membrane lipid composition
    Silvia Brambillasca
    CNR Institute of Neuroscience Cell Mol Pharmacology and Department of Medical Pharmacology, University of Milan, Milan, Italy
    EMBO J 24:2533-42. 2005
    ..These results identify the minimal requirements for transmembrane topogenesis of a TA protein and suggest that selectivity among various intracellular compartments can be imparted by differences in their lipid composition...
  41. ncbi request reprint Architecture of the ribosome-channel complex derived from native membranes
    Jean François Ménétret
    Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany St, Boston, MA 02118 2526, USA
    J Mol Biol 348:445-57. 2005
    ..Thus, we suggest that a single Sec61 complex may form a conduit for translocating polypeptides, while three copies of Sec61 play a structural role or recruit accessory factors such as TRAP...
  42. pmc Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosome
    Jean François Ménétret
    Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118 2526, USA
    Structure 16:1126-37. 2008
    ..Hence, this copy of Sec61 is positioned to capture and translocate the nascent chain. Finally, we show that mammalian and bacterial ribosome-channel complexes have similar architectures...
  43. pmc The role of p58IPK in protecting the stressed endoplasmic reticulum
    D Thomas Rutkowski
    Howard Hughes Medical Institute and Departments of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109 0650, USA
    Mol Biol Cell 18:3681-91. 2007
    ..These results identify a previously unanticipated location for p58(IPK) in the ER lumen where its putative function as a cochaperone explains the stress-sensitivity phenotype of knockout cells and mice...
  44. ncbi request reprint Conformational control through translocational regulation: a new view of secretory and membrane protein folding
    Vishwanath R Lingappa
    Department of Physiology, University of California, San Francisco, CA 94143 0444, USA
    Bioessays 24:741-8. 2002
    ....
  45. ncbi request reprint Transmembrane domain modulates sorting of membrane proteins in Toxoplasma gondii
    Verena Karsten
    Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 279:26052-7. 2004
    ..From these data, we conclude that although the TMD may not necessarily be a sole determinant in membrane protein sorting, its properties can markedly modulate the utilization of more conventional signal-mediated sorting pathways...
  46. pmc Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation
    Andrew L MacKinnon
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA
    J Am Chem Soc 129:14560-1. 2007
    ....
  47. pmc Mutant PrPSc conformers induced by a synthetic peptide and several prion strains
    Patrick Tremblay
    Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, California 94143, USA
    J Virol 78:2088-99. 2004
    ....