Our research is devoted to a molecular description of the process of membrane assembly and vesicular traffic in eukaryotic cells. Basic principles and approaches that we developed from studies on a simple eukaryote, Saccharomyces cerevisiae, are now being applied to investigate the mechanisms of intracellular vesicular traffic and the biogenesis and function of extracellular vesicles (exosomes) in cultured human cells.
Current Research
We have developed biochemical assays that measure the early events of polypeptide translocation into the endoplasmic reticulum (ER) and of vesicle-mediated protein transport from the ER to the Golgi apparatus. Vesicles formed in the transport reaction have an electron-dense,
In recent years, my research program has focused on the mechanism of unconventional secretion of proteins of physiologic interest such as IL-1 beta (8) and FABP4 (9). Most recently, we have become interested in the spread of α-synuclein (α-syn)
Current effort on α-syn,
An entirely distinct form of unconventional secretion invokes the capture of cytoplasmic proteins and small RNA molecules into vesicles exported into the extracellular medium in cultured cells or the extracellular fluids in metazoan organisms. Extracellular vesicles (EVs) form in two distinct pathways.
References
Annexin A6 mediates calcium-dependent exosome secretion during plasma membrane repair.
Williams JK*,Ngo JM*, Lehman IM, Schekman R. (*equal contribution)
Elife. 2023 May 19;12:e86556. doi: 10.7554/eLife.86556. PMID: 37204294.
Syncytin-mediated open-ended membrane tubular connections facilitate the intercellular transfer of cargos including Cas9 protein.
Zhang C, Schekman R.
Elife. 2023 Mar 10;12:e84391. doi: 10.7554/eLife.84391. PMID: 36896791.
Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers.
Wu S, Hernandez Villegas NC, Sirkis DW, Thomas-Wright I, Wade-Martins R, Schekman R.
Elife. 2023 Jan 10;12:e85837. doi: 10.7554/eLife.85837. PMID: 36626307.
Extracellular vesicles from neurons promote neural induction of stem cells through cyclin D1.
Song L, Tian X, Schekman R.
J Cell Biol. 2021 Sep 6;220(9):e202101075. doi: 10.1083/jcb.202101075. PMID: 34309628.
Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes.
Temoche-Diaz MM, Shurtleff MJ, Nottingham RM, Yao J, Fadadu RP, Lambowitz AM, Schekman R.
Elife. 2019 Aug 22;8:e47544. doi: 10.7554/eLife.47544. PMID: 31436530
Fatty-acid binding protein 5 modulates the SAR1 GTPase cycle and enhances budding of large COPII cargoes.
Melville D, Gorur A, Schekman R.
Mol Biol Cell. 2019 Feb 1;30(3):387-399. doi: 10.1091/mbc.E18-09-0548. PMID: 30485159.
TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers.
Yuan L, Kenny SJ, Hemmati J, Xu K, Schekman R.
Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12255-E12264. doi: 10.1073/pnas.1814810115. PMID: 30545919.
Extracellular Vesicles and Cancer: Caveat Lector.
Shurtleff MJ, Temoche-Diaz MM, Schekman R.
Annu Rev Cancer Bio. 2018 2:1, 395-411. doi: 10.1146/annurev-cancerbio-030617-050519.
Unconventional secretion of FABP4 by endosomes and secretory lysosomes.
Villeneuve J, Bassaganyas L, Lepreux S, Chiritoiu M, Costet P, Ripoche J, Malhotra V, Schekman R.
J Cell Biol. 2018 Feb 5;217(2):649-665. doi: 10.1083/jcb.201705047. PMID: 29212659.
Broad role for YBX1 in defining the small noncoding RNA composition of exosomes.
Shurtleff MJ*, Yao J*, Qin Y, Nottingham RM, Temoche-Diaz MM, Schekman R#, Lambowitz AM#. (*equal contribution, #co-corresponding authors)
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E8987-E8995. doi: 10.1073/pnas.1712108114. PMID: 29073095.
COPII-coated membranes function as transport carriers of intracellular procollagen I.
Gorur A*, Yuan L*, Kenny SJ, Baba S, Xu K, Schekman R. (*equal contribution)
J Cell Biol. 2017 Jun 5;216(6):1745-1759. doi: 10.1083/jcb.201702135. PMID: 28428367.
Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction.
Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R.
Elife. 2016 Aug 25;5:e19276. doi: 10.7554/eLife.19276.PMID: 27559612
Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion.
Zhang M, Kenny SJ, Ge L, Xu K, Schekman R.
Elife. 2015 Nov 2;4:e11205. doi: 10.7554/eLife.11205.PMID: 26523392
Phosphatidylinositol 3-kinase and COPII generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment.
Ge L, Zhang M, Schekman R.
Elife. 2014 Nov 28;3:e04135. doi: 10.7554/eLife.04135.PMID: 25432021
The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis.
Ge L, Melville D, Zhang M, Schekman R.
Elife. 2013 Aug 6;2:e00947. doi: 10.7554/eLife.00947.PMID: 23930225
Ubiquitin-dependent regulation of COPII coat size and function.
Jin L, Pahuja KB, Wickliffe KE, Gorur A, Baumgärtel C, Schekman R, Rape M.
Nature. 2012 Feb 22;482(7386):495-500. doi: 10.1038/nature10822.PMID: 22358839
COPII and the regulation of protein sorting in mammals.
Zanetti G, Pahuja KB, Studer S, Shim S, Schekman R.
Nat Cell Biol. 2011 Dec 22;14(1):20-8. doi: 10.1038/ncb2390.PMID: 22193160