Research Topics
Genomes and Genes | Ramanujan S HegdeSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Prion protein trafficking and the development of neurodegenerationRamanujan 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...- The surprising complexity of signal sequencesRamanujan 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.... 
The concept of translocational regulationRamanujan 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...- Quality and quantity control at the endoplasmic reticulumRamanujan 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... - Protein targeting and degradation are coupled for elimination of mislocalized proteinsTara 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... - The efficiency of protein compartmentalization into the secretory pathwayCorinna 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... - Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathwaySang-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... - Substrate-specific function of the translocon-associated protein complex during translocation across the ER membraneRyen 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... - Selective processing and metabolism of disease-causing mutant prion proteinsAarthi 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.... - A ribosome-associating factor chaperones tail-anchored membrane proteinsMalaiyalam 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... - Signal sequence insufficiency contributes to neurodegeneration caused by transmembrane prion proteinNeena 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... - Reduced translocation of nascent prion protein during ER stress contributes to neurodegenerationNeena 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... - Relocalization of STIM1 for activation of store-operated Ca(2+) entry is determined by the depletion of subplasma membrane endoplasmic reticulum Ca(2+) storeHwei 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... - Intracellular Ca(2+) release via the ER translocon activates store-operated calcium entryHwei 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... - Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteinsOishee 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.... - Retrotranslocation of prion proteins from the endoplasmic reticulum by preventing GPI signal transamidationAarthi 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... - Prion protein biosynthesis and its emerging role in neurodegenerationOishee 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... - Monitoring chaperone engagement of substrates in the endoplasmic reticulum of live cellsErik 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... - A calmodulin-dependent translocation pathway for small secretory proteinsSichen 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... 
The mechanism of membrane-associated steps in tail-anchored protein insertionMalaiyalam 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...- Identification of a targeting factor for posttranslational membrane protein insertion into the ERSandra 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... - Cotranslational partitioning of nascent prion protein into multiple populations at the translocation channelSoo Jung Kim
Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Biol Cell 13:3775-86. 2002.... - Membrane protein insertion at the endoplasmic reticulumSichen 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... - Compartment-restricted biotinylation reveals novel features of prion protein metabolism in vivoAmy 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... - The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cellsErik 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.... - Protection from cytosolic prion protein toxicity by modulation of protein translocationNeena 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... - Regulation of protein compartmentalization expands the diversity of protein functionKelly 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... - Formation of stacked ER cisternae by low affinity protein interactionsErik 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... - Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegenerationOishee 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... - Histone deacetylase inhibitors influence chemotherapy transport by modulating expression and trafficking of a common polymorphic variant of the ABCG2 efflux transporterAgnes 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... - In vitro dissection of protein translocation into the mammalian endoplasmic reticulumAjay 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... - Signal sequences control gating of the protein translocation channel in a substrate-specific mannerSoo Jung Kim
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892, USA
Dev Cell 2:207-17. 2002.... - Lighting up the stressed ERSang 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... - Targeting and beyond: new roles for old signal sequencesRamanujan 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... - Arginine 383 is a crucial residue in ABCG2 biogenesisOrsolya 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... - 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 - The role of p58IPK in protecting the stressed endoplasmic reticulumD 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... - Transmembrane domain modulates sorting of membrane proteins in Toxoplasma gondiiVerena 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... - Architecture of the ribosome-channel complex derived from native membranesJean 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... - Conformational control through translocational regulation: a new view of secretory and membrane protein foldingVishwanath R Lingappa
Department of Physiology, University of California, San Francisco, CA 94143 0444, USA
Bioessays 24:741-8. 2002.... - Transmembrane topogenesis of a tail-anchored protein is modulated by membrane lipid compositionSilvia 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... - A substrate-specific inhibitor of protein translocation into the endoplasmic reticulumJennifer 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... - Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosomeJean 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... - Mutant PrPSc conformers induced by a synthetic peptide and several prion strainsPatrick Tremblay
Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, California 94143, USA
J Virol 78:2088-99. 2004.... - Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocationAndrew L MacKinnon
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA
J Am Chem Soc 129:14560-1. 2007....