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Emr, Scott David
Frank H.T. Rhodes Class of '56 Endowed Director of the Weill Institute for Cell and Molecular Biology
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- Academic Director, Weill Inst for Cell & Mol Bio
- Professor, Molecular Biology and Genetics (MBG), College of Agriculture and Life Sciences (CALS)
- Adjunct Professor, Molecular Medicine (VETMM), College of Veterinary Medicine
Scott D. Emr is the Frank H.T. Rhodes Class of 1956 Professor of Molecular Biology and Genetics and Director of the Weill Institute for Cell and Molecular Biology). He receivedScott D. Emr is the Frank H.T. Rhodes Class of 1956 Professor of Molecular Biology and Genetics and Director of the Cornell Institute for Cell and Molecular Biology. He received his Ph.D. degree in Molecular Genetics from Harvard Medical School in 1981. Prior to joining the faculty at Cornell, he has held positions at the University of California, Berkeley (Miller Research Scholar; 1981-1983), the California Institute of Technology (Assistant and Associate Professor; 1983-1991) and the University of California, San Diego School of Medicine (Full Professor and Investigator in the Howard Hughes Medical Institute; 1991-2007). Dr. Emr counts among his early honors a Searle Scholars Award and an NSF Presidential Young Investigator Award. He has been elected a member of the National Academy of Sciences (2007), the American Academy of Arts and Sciences (2004) and the American Academy of Microbiology (1998). In 2003, he was awarded the Hansen Foundation Gold Medal Prize for elucidating intracellular sorting and transport pathways. In 2007, he was awarded the Avanti Prize for his key contributions in understanding lipid signaling pathways. He also serves as a member of the Advisory Board for the Pew Scholars Program in Biomedical Sciences supported by the Pew Charitable Trusts.
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Research
research overview
- Cell Signaling and Membrane Trafficking Our lab studies the regulation of cell signaling and membrane trafficking pathways by phosphoinositide kinases, protein kinases, selective ubiquitin modifications, and vesicle-mediated transport reactions. All eukaryotic cells maintain an elaborate system of vesicular transport pathways that convey cargo in and out of the cell via the endocytic and secretory systems. Our long-term goal has been to define the complex regulatory processes that ensure the temporal and spatial specificity of these membrane trafficking systems. We have focused our research in two major areas: (1) endocytic trafficking and receptor down-regulation and (2) phosphoinositide lipid- and ubiquitin-dependent membrane sorting pathways. Endocytosis and Receptor Down-Regulation The endosomal membrane trafficking system is required for many key cellular processes including down-regulation of activated cell-surface receptors, antigen presentation, and the sorting of biosynthetic cargoes to the lysosome. A subset of late endosomes contain internal vesicles and are referred to as multivesicular bodies (MVBs). MVB vesicles form by a membrane invagination process in which the vesicles bud into the lumen of the endosome. Our work has provided insights into the mechanism and regulation of this essential transport pathway. Entry of cargo into the MVB pathway, a highly regulated event, requires both cis- and trans-acting factors. Ubiquitination of endosomal membrane cargo proteins serves as a positive sorting signal for inclusion in the intralumenal MVB vesicle. We have identified and characterized more than a dozen transport components in the MVB-sorting pathway. Several of these proteins assemble into a set of protein-sorting complexes referred to as the ESCRT complexes I, II and III (endosomal sorting complexes required for transport), the sequential activities of which are required for the recognition and sorting of ubiquitin-modified MVB cargo proteins. Our observations indicate that both the phosphoinositide PI3P and monoubiquitin function as critical signals for the selective recruitment and activation of the endosomal sorting machinery required for receptor down-regulation. The mechanisms of assembly and function as well as the regulation of the ESCRT machinery are still poorly understood. Recently, we identified Mvb12 as a novel component of the ESCRT-I complex. Our data suggests that Mvb12, the first known regulator of the ESCRT complexes, maintains ESCRT-I in an inactive state in the cytosol and regulates the assembly of ESCRT-I and -II on the endosome, an essential step for cargo sorting in the MVB pathway. We have begun to address the molecular mechanisms that drive assembly and dynamics of the ESCRT-III lattice. ESCRT-III function is required for the final protein-sorting step and membrane invagination during MVB vesicle formation. Our results strongly indicate that the assembly of ESCRT-III on endosomes requires an activating conformational switch from an inactive cytoplasmic monomer. Of particular medical relevance, the ESCRT machinery has been shown to play an essential role in HIV viral budding. Topologically, the formation of MVB vesicles at the endosome and viral budding at the plasma membrane are similar. The ESCRT machinery therefore represents a new set of candidate targets for the development of antiviral drugs. Phosphoinositide Signaling and Membrane Trafficking We previously discovered that phosphoinositide (PI) lipids play an essential role in the regulation of membrane trafficking in both yeast and mammalian cells. PIs regulate diverse cellular processes, including cell growth, survival, differentiation, cytoskeletal organization, and membrane trafficking. Our long-term goal has been to understand how synthesis and turnover of PIPs (PI phosphates) are temporally and spatially regulated by lipid kinases and phosphatases. In addition, we have been using genetic and biochemical techniques to identify downstream targets/effectors for the structurally distinct PIPs. We have demonstrated that activation of the Vps34 PI 3-kinase results in production of the lipid second messenger PI3P which triggers the recruitment of FYVE domain and PX domain-containing effector proteins to endosomal membranes. These effectors regulate protein trafficking in the endosomal system. Likewise, we have shown that the essential phospholipid PI4,5P2 which is generated by the well-conserved PI4P 5-kinase Mss4 in yeast functions in the regulation of endocytosis and organization of the actin cytoskeleton. Based on these and other findings, it has become clear that PI lipids form part of a complex spatial code for defining organelle identity in eukaryotic cells. The PI lipids together with Rab GTPases and SNARE proteins function as spatial and temporal regulators of membrane trafficking. Pools of specific PI lipids (as well as certain other lipids like DAG) are enriched in compartments of the secretory and endocytic pathways. The basic compartmental "lipid code" that has been characterized thus far is composed of PI3P on membranes of the endosomal system, PI3,5P2 on the lysosome, PI4P on the Golgi complex and PI4,5P2 on the plasma membrane. Compartment-specific localization of PI kinases leads to restricted synthesis/localization of PIPs.† The organelle-restricted PIPs program the transport activity of the membrane by recruiting and activating specific effector proteins (containing domains such as PH, FYVE, PX, ENTH and GLUE domains) that directly bind the head group of the PI lipids. Our recent efforts have been directed at determining the mechanisms for the selective localization and regulation of the PI lipid kinases and phosphatases that are required to spatially restrict PI lipids to their appropriate compartment(s).
principal investigator on
- ESCRTING RECEPTORS FOR DEGRADATION awarded by AMERICAN CANCER SOCIETY 2012 - 2014
- SUBSTRATE TARGETING MECHANISMS OF NEDD4 FAMILY UBIQUITIN LIGASES awarded by NATL INST OF GENERAL MEDICAL SCIENCES, NIH 2012 - 2014
area(s) of concentration/expertise
keywords
- Cell biology
- Cell signaling
- Membrane trafficking
Publications
individual publications
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academic article
- ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology. . Developmental Cell. 23:1129-1140. 2012
- The Endosomal sorting complex ESCRT-II mediates the assembly and architecture of ESCRT-III helices.. Cell. 151:356-371. 2012
- The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P2 synthesis at the plasma membrane.. EMBO Journal. 31:2882-2894. 2012
- Ubiquitin and membrane protein turnover: from cradle to grave.. Annual Review Biochemistry. 81:231-259. 2012
- Ubiquitinated Cargo is Essential for the ESCRT-dependent Formation of Multivesicular Body Intralumenal Vesicals. EMBO Journal. 13:331-338. 2012
- Eisosome proteins assemble into a membrane-organizing scaffold.. Journal of Cell Biology. 195:889-902. 2011
- Genetic interactions with mutations affecting septin assembly reveal ESCRT functions in budding yeast cytokinesis. Biological Chemistry. 392:699-712. 2011
- Osh Proteins Regulate Phosphoinositide Metabolism at Membrane contact sites. Cell. 144:389-401. 2011
- Osh proteins regulate phosphoinositide metabolism ER-plasma membrane contact sites. Cell. 144:389-401. 2011
- Phosphoinositide (PI(3,5)P2) lipid-dependent regulation of the general transcriptional regulator Tup1. Genes and Development. 25:984-995. 2011
- TORC1 regulates endocytosis via Npr1-mediated Phosphoinhibition of a ubiquitin ligase adaptor. Cell. 147:1104-1117. 2011
- The ESCRT Pathway. Developmental Cell. 21:77-91. 2011
- The ORP protein family activates the Sac1 phosphoinositide phosphatase at ER-plasma membrane contact sites. Cell. 144:389-401. 2011
- Two novel WD40 domain-containing proteins, Ere1 and Ere2, function in the retromer-mediated endosomal recycling pathway. Molecular Biology of the Cell. 22:4093-4107. 2011
- Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function. EMBO Journal. 29:1489-1498. 2010
- ESCRT-II coordinates the assembly of ESCRT-III finalments required for cargo sorting and multivesicular body vesicle formation. EMBO Journal. 29:871-883. 2010
- Pheremone-induced anisotropy in yeast plasma membrane phosphatidylinositol-4,5-bisphosphate distribution is required for MAPK signaling. Proceedings of the National Academy of Sciences of the United States of America. 107:11805-11810. 2010
- Cargo sorting into multivesicular bodies in vitro. . Proceedings of the National Academy of Sciences of the United States of America. 106:17395-400. 2009
- ESCRTs and human disease. Biochemical Society Transactions. 37:167-72. 2009
- Functional reconstitution of ESCRT-III assembly and disassembly. Cell. 136:97-709. 2009
- Journeys through the Golgi--taking stock in a new era. Journal of Cell Biology. 187:449-53. 2009
- Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. . Cell. 135:714-725. 2008
- Assembly of a Fab1 phosphoinositide kinase signaling complex requires the Fig4 phosphoinositide phosphatase. . Molecular and Cellular Biology. 19:4273-4286. 2008
- Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3.. Journal of Cell Biology. 183:1061-1074. 2008
- Novel Ist-1-Did2 complex functions at a late step in MVB sorting.. Molecular Biology of the Cell. 19:475-484. 2008
- Ordered assembly of the ESCRT-III complex on endosomes is required to sequester cargo during MVB formation.. Developmental Cell. 15:578-589. 2008
- Structure and disassembly of filaments formed by the ESCRT-III subunit Vps24.. Structure. 16:1345-1356. 2008
- Atg18 regulates organelle morphology and fab1 kinase activity independent of its membrane recruitment by phosphatidylinositol 3,5-bisphosphate. Molecular Biology of the Cell. 18:4232-4244. 2007
- ESCRTing proteins in the endocytic pathway. Trends in Biochemical Sciences. 32:561-573. 2007
- Structural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4. Nature. 449:735-739. 2007
- Structural insight into the ESCRT-I/-II super-complex and its interaction networks on membranes. EMBO Journal. 26:600-612. 2007
- Structural studies of phosphoinositide 3-kinase dependent traffic to multivesicular bodies. Biochemical Society Symposia. 74:47-57. 2007
- New component of ESCRT-I regulates endosomal sorting complex assembly. Journal of Cell Biology. 175:815-823. 2006
- Structural and functional organization of the ESCRT-I trafficking complex. Cell. 125:113-126. 2006
- Structures of the ESCRT-I core and the ESCRT-II GLUE domain: central role for GLUE domain in direct linking to ESCRT-I, phosphoinositides and ubiquitin. Cell. 125:99-111. 2006
- TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF. Nature Cell Biology. 8:1263-1269. 2006
- The ESCRT complexes: structure and mechanism of a membrane-trafficking network. Annual Review of Biophysics and Biomolecular Structure. 35:277-298. 2006
- The PI4,5P2 effectors Slm1 and Slm2 link calcineurin and sphingolipid signaling pathway. Molecular and Cellular Biology. 26:5861-5875. 2006
- PI 3-phospate accumulation in triple lipid phosphatase-deletion mutants triggers lethal hyper-activation of the Rho1p/Pkc1p cell integrity MAP kinase pathway. Journal of Cell Science. 118:5589-5601. 2005
- Pathogen Effector Protein Screening in Yeast identifies Legionella factors that interfere with membrane trafficking. Proceedings of the National Academy of Sciences of the United States of America. 102:4866-4871. 2005
- Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway. Molecular Biology of the Cell. 16:776-793. 2005
- The Fab1 phosphatidylinositol kinase pathway in the regulation of vacuole morphology. Current Opinion in Cell Biology. 4:402-408. 2005
- The Phosphoinositide Phosphatase Sjl2 Is Recruited to Cortical Actin Patches in the Control of Vesicle Formation and Fission. Molecular and Cellular Biology. 25:2910-2923. 2005
- Yeast Mon2p is a highly conserved protein that functions in the cytoplasm-to-vacuole transport pathway and is required for Golgi homeostasis. Journal of Cell Science. 1118:4751-4764. 2005
- Cytoplasmic IP6 production is sufficient for mediating the Gle1-mRNA export pathway. Journal of Biological Chemistry. 279:51022-51032. 2004
- Essential role for the myotubularin-related phosphatase Ymr1p and the synaptojanin-like phosphatases Sjl2P and Sjl3P in the regulation of phosphatidylinositol 3-phosphate in yeast. Molecular Biology of the Cell. 15:3567-3579. 2004
- Genome-wide Lethality Screen Identifies New PI4,5P2 Effectors that regulat the Actin Cytoskeleton. EMBO Journal. 23:3747-3757. 2004
- Genome-wide analysis of membrane targeting by S. cerevisiae pleckstrin homology domains. Molecular Cell. 13:677-688. 2004
- Structure of the ESCRT-II endosomal trafficking complex. Nature. 9:221-225. 2004
- Ubiquitin interactions of NZF zinc fingers. EMBO Journal. 23:1411-1421. 2004
- Varshavsky’s contributions. Science. 306:1290-1292. 2004
- A unified nomenclature for yeast autophagy-related genes. Developmental Cell. 5:539-545. 2003
- Bro1 is an endosome-associated class E Vps protein that functions in the MVB-sorting pathway in Saccharomyces cerevisiae. Journal of Cell Science. 116:1893-2003. 2003
- Multivesicular body sorting: Ubiquitin ligase Rsp5 is required for the modification and sorting of carboxypeptidase S. Molecular Biology of the Cell. 15:468-480. 2003
- Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO Journal. 22:4223-4236. 2003
- Vacuole size control: Regulation of PtdIns(3,5)P2 levels by the vacuole-associated Vac14-Fig4 complex, a PtdIns(3,5)P2-specific phosphatase. Molecular Biology of the Cell. 15:24-36. 2003
- Vps27 recruits ESCRT machinery to endosomes during MVB sorting. Journal of Cell Biology. 160:413-423. 2003
- Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13 and Cvt20, to PtdIns(3)P at the pre-autophagosomal structure is required for selective autophagy. Journal of Biological Chemistry. 277:30198-30207. 2002
- ESCRT-III: An endosome-associated heterooligomeric protein complex required for MVB sorting. Developmental Cell. 3:271-282. 2002
- Endosomal localization and function of sorting nexin 1. PNAS. 10:6767-6772. 2002
- Endosome-associated complex, ESCRT-II, Recruits transport machinery for protein sorting at the multivesicular body. Developmental Cell. 3:283-289. 2002
- Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nat. Cell. Biol.. 4:389-393. 2002
- Novel PI(3)P Binding Protein, Etf1, Required for Autophagy in Yeast. Journal of Cell Biology. 158:761-772. 2002
- Osmotic stress-induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p. Journal of Cell Biology. 18:1015-1028. 2002
- Receptor Downregulation and Multivesicular-Body Sorting. Molecular and Cellular Biology. 3:893-905. 2002
- Regulation of Fab1 phosphatidylinositol 3-phosphate 5-kinase pathway by Vac7 protein and Fig4, a polyphosphoinositide phosphatase family member. Molecular Biology of the Cell. 13:1238-1251. 2002
- Retromer function in endosome-to Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase. Journal of Cell Science. 115:3889-3900. 2002
- Rothman and Schekman SNAREd by Lasker for Trafficking. Cell. 111:1-3. 2002
- Stt4 PtdIns 4-kinase Localizes to the Plasma Membrane and Functions in the Pkc1-mediated MAP kinase cascade. Developmental Cell. 2:593-605. 2002
- The Saccharomyes cerevisiae LSB6 Gene Encodes Phosphatidylinositol 4-kinase Activity. Journal of Biological Chemistry. 277:47709-47718. 2002
- The Yeast Synaptojanin-like proteins control the cellular distribution of phosphatidylinositol(4,5)-bisphosphate. Molecular Biology of the Cell. 13:542-557. 2002
- Location, Location, Location: Membrane Targeting Directed by PX domains. Science. 294:1881-1885. 2001
- Phox domain interaction with PtdIns(3)P targets the Vam7 t-SNARE to vacuole membranes. Nature Cell Biology. 3:613-618. 2001
- Sac1 lipid phosphatase and Stt4 PtdIns 4-kinase regulate a pool of PtdIns(4)P that functions in the control of the actin cytoskeleton and vacuole morphology. Molecular Biology of the Cell. 12:2396-2411. 2001
- The class C Vps complex functions at multiple stages of the vacuolar transport pathway. Traffic. 2:476-486. 2001
- The role of phosphoinositides in membrane transport. Current Opinion in Cell Biology. 13:485-492. 2001
- Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 106:145-155. 2001
- Yeast GGA Proteins Function with Clathrin in Golgi to Endosome Transport. Molecular Biology of the Cell. 12:1885-1896. 2001
- Autophagy as a regulated pathway of cellular degradation. Science. 290:1717-1721. 2000
- Class C Vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion. Molecular Cell. 6:661-671. 2000
- Distinct roles for the yeast PtdIns 4-kinases, Stt4p and Pik1p, in secretion, cell growth and organelle dynamics. Molecular Biology of the Cell. 8:2673-2689. 2000
- New component of the vacuolar class C Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent Docking/Fusion. Journal of Cell Biology. 151:551-562. 2000
- Phosphoinositide signaling and the regulation of membrane trafficking. Trends in Biol. Sci.. 25:229-235. 2000
- Tumor susceptibility gene TSG101 functions in receptor tyrosine-kinase trafficking and down-regulation. Traffic. 1:248-258. 2000
- Characterization of the Rab-binding region of guanine nucleotide dissociation inhibitor (Gdi1p) in Saccaromyces cerevisiae. Journal of Biological Chemistry. 274:14806-14817. 1999
- Cytoplasm to vacuole trafficking of Aminopeptidase I requires t-SNARE/Sec1p complex composed of Tlg2p and Vps45p. EMBO Journal. 18:6005-6016. 1999
- Formation of AP-3 transport intermediates requires Vps41 function. Nature. 1:346-353. 1999
- Identification of a novel domain shared by putative components of the endocytic and cytoskeletal machinery. Protein Science. 8:435-438. 1999
- Ligand recognition and domain structure of Vps10p, a vacuolar protein sorting sorting receptor in Saccharomyces cerevisiae. Eur. J. Biochem.. 260:461-469. 1999
- MCD4 encodes a conserved ER membrane protein essential for GPI anchoring in yeast. Molecular and Cellular Biology. 10:627-648. 1999
- Phosphatidylinositol 3-phosphate recognition by the FYVE domain. Molecular Cell. 3:805-811. 1999
- Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways. Journal of Biological Chemistry. 274:9129-9132. 1999
- Vac1p coordinates rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. Current Biology. 9:159-62. 1999
- Yeast epsins contain an essential N-terminal ENTH domain, bind clathrin, and are required for endocytosis. EMBO Journal. 18:4383-4393. 1999
- A membrane coat complex essential for endosome to Golgi retrograde transport in yeast. Journal of Cell Biology. 142:665-681. 1998
- ARF is required for maintenance of yeast Golgi and endosome structure and function. Molecular and Cellular Biology. 9:653-670. 1998
- Acidic di-leucine motif essential for AP-3 dependent sorting and restriction of the functional specificity of the Vam3p vacuolar t-SNARE. Journal of Cell Biology. 142:913-922. 1998
- COPI in ER/Golgi and intra-Golgi transport: do yeast COPI mutants point the way. BBA-Molecular Cell Research. 1401:33-51. 1998
- Fab1p PtdIns(3)P 5-kinase essential for protein sorting in the multivesicular body. Cell. 95:847-858. 1998
- Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. Journal of Cell Biology. 143:65-79. 1998
- Novel pathways, membrane coats and PI Kinase regulation in yeast lysosomal trafficking. Seminars in Cell and Dev. Biol.. 9:527-533. 1998
- Pan1p, yeast eps15, functions as a multivalent adaptor that coordinates protein-protein interactions essential for endocytosis. Journal of Cell Biology. 141:71-84. 1998
- Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains. Molecular Cell. 2:157-162. 1998
- Phosphoinositide signaling and turnover: PtdIns(3)P, a regulator of membrane traffic, is transported to the vacuole and degraded by a process that requires lumenal vacuolar hydrolase activities. EMBO Journal. 17:4930-4942. 1998
- Protein Traffic in the yeast endocytic and vacuolar protein sorting pathways. Current Opinion in Cell Biology. 10:513-522. 1998
- The AP-3 complex: A coat of many colours. Trends in Cell Biol.. 8:282-288. 1998
- The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO Journal. 17:101-112. 1998
- Vam7p, a SNAP25-like molecule, and Vam3p, a Syntaxin homolog, function together in yeast vacuolar protein trafficking. Molecular and Cellular Biology. 18:5308-5319. 1998
- A multi-specificity syntaxin homologue, Vam3p, essential for autophagic and biosynthetic protein transport to the vacuole. Journal of Cell Biology. 138:517-529. 1997
- A novel RING-finger protein complex essential for a late step in protein transport to the yeast vacuole. Molecular Biology of the Cell. 8:2307-2327. 1997
- A novel Sec18p/NSF-dependent complex required for Golgi to endosome transport in yeast. Molecular and Cellular Biology. 8:1089-1104. 1997
- A sorting nexin-1 homologue, Vps5p, forms a complex with Vps17p and is required for recycling the vacuolar protein sorting receptor. Molecular Biology of the Cell. 8:1529-1541. 1997
- COPI-independent anterograde transport of specific secretory proteins in yeast. Journal of Cell Biology. 136:789-802. 1997
- Characterization of VPS41, a gene required for vacuolar trafficking and high-affinity iron transport in yeast. Proceedings at the National Academy of Science USA. 94:5662-5666. 1997
- Disruption of three phosphatidylinositol polyphosphate 5-phosphatase genes from Saccharomyces cerevisiae results in pleiotropic abnormalities of vacuole morphology, cell shape, and osmohomeostasis. European Journal of Cell Biology. 74:350-360. 1997
- Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30 and VPS35 gene products. Journal of Cell Biology. 137:79-92. 1997
- Endosome transport function in yeast requires novel AAA-type ATPase, Vps4p. EMBO Journal. 16:1820-1831. 1997
- Membranes and sorting.. Current Opinion in Cell Biology. 9:475-476. 1997
- Novel Golgi to vacuole delivery pathway in yeast: identification of a sorting determinant and required transport component. EMBO Journal. 16:2769-2782. 1997
- Regulation of the Saccharomyces cerevisiae Vps34p Phosphatidylinositol 3-kinase. FASEB Journal. 25:1141-1146. 1997
- The AP-3 adaptor complex is essential for cargo-selective transport to the yeast vacuole. Cell. 91:109-118. 1997
- A novel FACS-based screen for yeast endocytosis mutants identifies a yeast homolog of mammalian eps15. Journal of Cell Biology. 135:1485-1500. 1996
- A novel RING-finger protein, Vps8p, functionally interacts with the small GTPase, Vps21p, to facilitate soluble vacuolar protein localization. Journal of Biological Chemistry. 271:33607-33615. 1996
- A yeast protein related to a mammalian Ras binding protein, Vps9p, is required for localization of vacuolar proteins. Molecular and Cellular Biology. 16:2369-2377. 1996
- Multilamellar endosome-like compartment accumulates in the yeast vps28 vacuolar protein sorting mutant. Molecular and Cellular Biology. 7:985-999. 1996
- Multiple pathways for vacuolar sorting of yeast proteinase A. Journal of Biological Chemistry. 271:11865-11870. 1996
- Novel syntaxin homologue, Pep12p, required for hydrolase sorting to the lysosome-like vacuole in yeast. Molecular and Cellular Biology. 7:579-594. 1996
- Phosphoinositides as key regulators in membrane traffic. Science. 271:1533-1539. 1996
- Receptor signalling and the regulation of endocytic membrane transport. Current Opinion in Cell Biology. 8:549-556. 1996
- A new vital stain for monitoring vacuolar membrane dynamics and endocytosis in yeast. Journal of Cell Biology. 128:779-792. 1995
- Identification and characterization of a Vps34p-like phosphatidylinositol 3-kinase in Schizosaccharomyces pombe. Journal of Cell Science. 108:3745-3756. 1995
- Novel PI(4)P 5-kinase homologue, Fab1p, essential for normal vacuole function and morphology in yeast. Molecular Biology of the Cell. 6:525-539. 1995
- Phosphatidylinositol kinase gene family in Dictyostelium discoideum: Biological roles of putative mammalian p110 and yeast Vps34p PI 3-kinase homologues during growth and development. Molecular and Cellular Biology. 15:5645-5656. 1995
- Protein transport to the yeast vacuole. Current Opinion in Cell Biology. 7:544-551. 1995
- Receptor-mediated protein sorting to the vacuole in yeast: Roles for a protein kinase, a lipid kinase and GTP-binding proteins. Ann. Rev. Cell Dev. Biol.. 11:1-33. 1995
- Role for phosphatidylinositol 3-kinase in the sorting and transport of newly synthesized lysosomal enzymes in mammalian cells. Journal of Cell Biology. 130:781-796. 1995
- The cytoplasmic tail domain of the vacuolar protein sorting receptor Vps10p and a subset of VPS gene products regulate receptor stability, function and localization. Molecular Biology of the Cell. 6:1089-1102. 1995
- Vesicle-mediated protein transport: Regulatory interactions between the Vps15 protein kinase and the Vps34 PtdIns 3-kinase essential for vacuolar protein transport. Journal of Cell Biology. 129:321-334. 1995
- AtVPS34, a phosphatidylinositol 3-kinase of Arabidopsis thaliana, is an essential protein with homology to a calcium-dependent lipid binding domain. Proceedings at the National Academy of Science USA. 91:11398-11402. 1994
- Clathrin-dependent localization of a 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae. Journal of Cell Biology. 127:667-678. 1994
- Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum. Cell. 79:1199-1207. 1994
- Mammalian phosphatidylinositol 3'-kinase is functionally distinct from the related Saccharomyces cerevisiae VPS34 gene product. Eur. J. Biochem.. 219:775-780. 1994
- Mutations in the VPS45 gene, a SEC1 homologue, result in vacuolar protein sorting defects and accumulation of membrane vesicles. Journal of Cell Science. 107:3449-3459. 1994
- Signal-mediated retrieval of a membrane protein from the Golgi to the ER in yeast. Journal of Cell Biology. 127:653-665. 1994
- The sorting receptor for yeast carboxypeptidase Y is encoded by the VPS10 gene. Cell. 77:579-586. 1994
- VPS21 encodes a rab5-like GTP-binding protein required for the sorting of yeast vacuolar proteins. EMBO Journal. 13:1297-1309. 1994
- Vps34p Required for yeast vacuolar protein sorting is a multiple specifity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities. Journal of Biological Chemistry. 269:31552-31562. 1994
- A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO Journal. 12:2195-2204. 1993
- Brefeldin A reversibly blocks early but not late protein transport steps in the yeast secretory pathway. EMBO Journal. 12:869-877. 1993
- Genetic and biochemical studies of protein sorting to the yeast vacuole. Current Opinion in Cell Biology. 5:641-646. 1993
- Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science. 260:88-91. 1993
- The VPS16 gene product associates with a sedimentable protein complex and is essential for vacuolar protein sorting in yeast. Journal of Biological Chemistry. 268:4953-4962. 1993
- The yeast VPS17 gene encodes a membrane-associated protein required for the sorting of soluble vacuolar hydrolases. Journal of Biological Chemistry. 268:559-569. 1993
- Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment. Journal of Cell Biology. 121:1245-1256. 1993
- Alternative pathways for the sorting of soluble vacuolar proteins in yeast: A vps35 null mutant missorts and secretes only a subset of vacuolar hydrolases. Molecular and Cellular Biology. 3:415-427. 1992
- An essential role for a protein and lipid kinase complex in secretory protein sorting. Trends in Cell Biology. 2:363-368. 1992
- In vitro reactions of vacuole inheritance in Saccharomyces cerevisiae. Journal of Cell Biology. 119:1469-1479. 1992
- A genetic and structural analysis of the yeast Vps15 protein kinase: Evidence for a direct role of Vps15p in vacuolar protein delivery. EMBO Journal. 10:4049-4060. 1991
- A novel protein kinase homolog is required for protein sorting to the yeast lysosome-like vacuole. Cell. 64:425-437. 1991
- Compartmental organization of Golgi-specific protein modification and vacuolar protein sorting events defined in a yeast sec18 (NSF) mutant. Journal of Cell Biology. 114:207-218. 1991
- Heat shock proteins can substi¬tute for SecB function during protein export in Escherichia coli. EMBO Journal. 10:239-245. 1991
- Mitochondrial protein import: Isolation and characterization of the Saccharomyces cerevisiae MTF1 gene. Mol. Gen. Genetics. 225:483-491. 1991
- Putative zinc finger protein, the Saccharomyces cerevisiae Vps18p, affects late Golgi functions required for valuolar protein sorting and efficient -factor prohormone maturation. Molecular and Cellular Biology. 12:5813-5824. 1991
- A new class of lysosomal/vacuolar protein sorting signals. Journal of Biological Chemistry. 265:5349-5352. 1990
- Characterization of VPS34, a gene required for vacuolar protein sorting and vacuole segregation yeast. Molecular and Cellular Biology. 10:6742-6754. 1990
- Characterization of a region in mature LamB protein that interacts with a component of Escherichia coli's export machinery. Journal of Biological Chemistry. 265:18148-18153. 1990
- Characterization of the yeast Vps33p, a protein required for vacuolar protein sorting and vacuole biogenesis. Molecular and Cellular Biology. 10:4638-4649. 1990
- In vitro reconstitution of intercompart-mental protein transport to the yeast vacuole. Journal of Cell Biology. 112:2871-2884. 1990
- Mutants of Saccharomyces cerevisiae that block intervacuole vesicular traffic and vacuole division and segregation. Proceedings at the National Academy of Science USA. 87:1076-1080. 1990
- The fungal vacuole: Composition, function, and biogenesis. Microbio. Rev.. 54:266-292. 1990
- The presence of both the signal sequence and a region of mature LamB protein are required for the interaction of LamB with the export factor SecB. Journal of Biological Chemistry. 265:18154-18160. 1990
- Membrane protein sorting: Biosynthesis, transport, and processing of yeast vacuolar alkaline phosphatase. EMBO Journal. 8:2241-2250. 1989
- Sequence and structural requirements of a mitochondrial protein import signal defined by saturation cassette mutagenesis. Molecular and Cellular Biology. 9:1014-1025. 1989
- The Saccharomyces cerevisiae SEC14 gene encodes a cytosolic factor that is required for transport of secretory proteins from the yeast Golgi complex. Journal of Cell Biology. 108:1271-1281. 1989
- Characterization of a component of the yeast secretion machinery: Identification of the SEC18 gene product. Molecular and Cellular Biology. 8:4098-4109. 1988
- Organelle assembly: Characterization of yeast mutants defective in vacuole biogenesis and protein sorting. Journal of Cell Biology. 107:1369-1383. 1988
- Protein sorting and organelle biogenesis in yeast. Cell Technology (Tokyo). 2:84-91. 1987
- GAL2 codes for a membrane-bound subunit of the galactose permease in Saccharomyces cerevisiae. Journal of Bacteriology. 166:313-318. 1986
- Isolation of yeast mutants defective in protein sorting to the vacuole. Proceedings at the National Academy of Science USA. 83:9075-9079. 1986
- The amino terminus of the yeast F1-ATPase -subunit precursor functions as a mito-chondrial import signal. Journal of Cell Biology. 102:523-533. 1986
- Invertase signal and mature sequence substitutions that delay intercompartmental transport of active enzyme. Journal of Cell Biology. 100:1664-1675. 1985
- D-ribose metabolism in Escherichia coli K-12: Genetics, regulation, and transport. Journal of Bacteriology. 158:665-673. 1984
- Intracellular targeting and import of an ATP2-lacZ fusion protein into yeast mitochondria. Proceedings at the National Academy of Science USA. 81:3983-3987. 1984
- Invertase--galactosidase hybrid proteins fail to be transported from the endoplasmic reticulum in yeast. Molecular and Cellular Biology. 4:2347-2355. 1984
- An MF1-SUC2 (-factor-Invertase) gene fusion for study of protein localization and gene expression in yeast. Proceedings at the National Academy of Science USA. 80:7080-7084. 1983
- Mechanisms of protein localization. Microbiol. Rev.. 47:313-344. 1983
- The importance of secondary structure in the signal sequence for protein secretion. Proceedings at the National Academy of Science USA. 80:4599-4603. 1983
- A previously unidentified gene in the spc operon of Escherichia coli K12 specifies a component of the protein export machinery. Cell. 31:227-235. 1982
- Genetic approaches to study export of LamB to the outer membrane. Ann. Microbiol. (Paris). 133a:115-122. 1982
- Localization and processing of outer membrane and periplasmic proteins in Escherichia coli strains harboring export-specific suppressor mutations. Journal of Biological Chemistry. 257:5852-5860. 1982
- Molecular components of the signal sequence that function in the initiation of protein export. Journal of Cell Biology. 95:689-696. 1982
- Suppressor mutations that restore export of a protein with a defective signal sequence. Cell. 23:79-88. 1981
- Genetic studies on mechanisms of protein localization in Escherichia coli K-12. J. Supramol. Struct.. 13:147-163. 1980
- Mutations affecting localization of an Escherichia coli outer membrane protein, the bacteriophage receptor. Journal of Molecular Biology. 141:63-90. 1980
- Sequence analysis of mutations that prevent export of receptor, an Escherichia coli outer membrane protein. Nature. 285:82-85. 1980
- aA mechanism of protein localization: the signal hypothesis and bacteria. Journal of Cell Biology. 86:701-711. 1980
- Mutations altering the cellular localization of the receptor: An Escherichia coli outer membrane protein. Proceedings at the National Academy of Science USA. 75:5802-5806. 1978
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article
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book
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booksection
- Vacuoles, Cell Architecture and Function. Vol. 4. 2004
- FYVE Domains in Membrane Trafficking and Cell Signaling. Vol. 2. 2003
- Isolation of subcellular fractions from the yeast Saccharomyces cerevisiae 2000
- Overview of subcellular fractionation procedures for the yeast Saccharomyces cerevisiae 2000
- Vacuolar protein sorting-specific protein kinase 1995
- Vacuolar protein sorting in yeast. Vol. H 71. 1993
- A protein kinase/lipid kinase complex required for yeast vacuolar protein sorting. Vol. H74. 1992
- Heterologous gene expression in yeast. Vol. 185. 1990
- Protein sorting in the yeast secretory pathway. Vol. 125. 1990
- Mutational analysis of the yeast F1-ATPase -subunit mitochondrial protein import signal: Evidence of functional redundancy 1988
- Vacuolar protein targeting and organelle biogenesis in yeast 1988
- A genetic approach to study protein sorting and organelle assembly in yeast. Vol. III. 1987
- Plasma membrane assembly in yeast 1987
- Export and Localization of Escherichia coli envelope proteins 1986
- The signal hypothesis in bacteria 1982
- The genetics of protein secretion in Escherichia coli 1980
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chapter
- FYVE Domains in Membrane Trafficking and Cell Signaling. Handbook of Cell Signaling (second edition). 1111-1122. 2009
- Protein synthesis and posttranslational modifications. . Chapter 3. The Genetics of Protein Secretion in Escherichia coli. Methods Cell Biol.. 27-38. 1981
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conference paper
- Structural studies of phosphoinositide 3-kinase dependent traffic to multivesicular bodies. Biochem. Soc. Symp.. 47-57. 2007
- Novel protein kinase/phosphatidylinositol 3-kinase complex essential for receptor-mediated protein sorting to the vacuole in yeast. CSH Symposium on Quantitative Biology. 1995
- Secretion and organelle assembly in yeast. Gene Expression in Yeast, Proceed. ALKO Symp.. 1983
- The use of gene fusions to study outer membrane protein localization. Limited Proteolysis in Microorganisms. 1979
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document part
-
report
- Gene fusions to study intracellular protein traffic and organelle assembly in yeast 1985
- Hybrid protein delivery and import into yeast mitochondria 1985
- Import of ATP2-lacZ gene fusion proteins into mitochondria 1983
- The mechanism of secretion of proteins in Escherichia coli 1979
- The use of gene fusion to study protein localization in Escherichia coli 1979
featured in archived article
- A major hire to advance and extend life sciences at Cornell
- At Weill Hall dedication, faculty panel ponders life science feats and promises
- Cornell professors Scott Emr and Richard Durrett elected to National Academy of Sciences
- Emr elected associate member of elite European Molecular Biology Organization
- For researchers in Weill Hall, collaboration between Ithaca and New York City is central
- New Institute of Cell and Molecular Biology will raise stature of cell biology on Cornell campus
- Researchers describe how cells take out the trash to prevent disease
- Researchers uncover how protein receptors on cells switch on and off for growth and health
- Scott Emr to lead biology institute at Cornell
- Study uncovers key mechanisms of cell communication
- Weill Hall and institute dedicated in celebration of 'an icon for our future'
- Weill Hall, life science research center for ideas and collaboration, is open for business
Service
service to the profession
- ASCB - EB Wilson Medal Selection Committee Committee Member 2006 -
- American Society for Cell Biology Council Member 2006 -
- Eli Lilly Research Award Nominating Committee Committee Member 2005 -
- Academic Senate, University of California, San Diego Departmental Representative 2004 -
- Core Curriculum Committee, Biomedical Sciences Graduate Program, UCSD School of Medicine Chairperson 2004 -
- Graduate Planning Committee, Biomedical Sciences Graduate Program, UCSD School of Medicine Committee Member 2004 -
- Pew Scholars Program Advisory Board and Review Panel Board of Advisors 2003 -
- Executive Committee, Biomedical Science Graduate Program, UCSD School of Medicine Member 1999 -
- Executive Committee, Center for Molecular Genetics, UCSD Committee Member 1999 -
- Core Committee, Biomedical Sciences Graduate Program, UCSD School of Medicine Committee Member 1996 -
- Center for Molecular Genetics, UCSD Member 1991 -
- Graduate Council, UCSD Academic Senate Vice-chair 2003 - 2004
- Biomedical Sciences Graduate Program, UCSD Co-Chair 2001 - 2002
- Gordon Research Conference on Lysosomes, Proctor Academy, NH Chairperson - 2002
- Biomedical Sciences Graduate Program, UCSD Vice-Chair 1999 - 2001
- Scientific Organizing Committee; Fourth International AAA-Type ATPase Conference Committee Member 1999 - 2001
- Scientific Organizing Committee; XXth International Symposium on Yeast Genetics and Molecular Biology Committee Member 1999 - 2001
- Standing Promotions Advisory Committee, UCSD Chairperson 1999 - 2001
- Graduate Admissions Committee, Biomedical Sciences Graduate Program, UCSD School of Medicine Member 1991 - 2000
- Gordon Research Conference on Lysosomes Vice-Chair - 2000
- Program Committee; 1999 ASCB Annual Meeting Committee Member 1998 - 1999
- Graduate Admissions Committee, Biomedical Sciences Graduate Program, UCSD School of Medicine Chairperson 1997 - 1999
- Radiation Safety and Surveillance Committee, UCSD Academic Senate Chairperson 1996 - 1999
- Department of Cellular and Molecular Medicine Seminar Program, UCSD School of Medicine Chairperson 1992 - 1997
- FASEB Research Conferences Advisory Committee Committee Member 1994 - 1996
- Division of Biology Graduate Policy Committee, Caltech Chairperson 1989 - 1991
- Division of Biology Graduate Program, Caltech Chairperson 1989 - 1991
- Graduate Admissions Committee, Division of Biology, Caltech Member 1984 - 1991
- Molecular, Cellular and Developmental Biology Seminar Program, Division of Biology, Caltech Chairperson 1986 - 1989
reviewer or editor for
event host
Background
education and training
- Ph.D. in Microbiology & Molecular Genetics, Harvard University 1981
- University of Rhode Island 1976
awards and honors
- Elected Associate Member, 2008
- Elected Member, 2007
- Avanti Award for "key contributions in lipid signaling research", 2007
- Elected Member, 2004
- Gold Medal Prize for "central role in elucidating the intracellular sorting and transport of proteins", 2003
- Elected Fellow, 2000
- Elected Fellow, 1998
- Investigator (1991-2007), 1991
- Presidential Young Investigator Award (1985-1990), 1985
- Searle Scholar Award (1984-1987), 1984
- Miller Research Institute Fellow (1981-1983), 1981
- Phi Kappa Phi, 1975
Other
college
- CALS
research keyword
- Cell biology
- Cell signaling
- Membrane trafficking
name prefix
- Professor