Vladimir V. Lupashin
Ph.D., Russian Academy of Sciences
Office: (501) 603-1170
Lab: (501) 603-1171
Our laboratory is interested in understanding the molecular mechanisms responsible for the generation and maintenance of intra-cellular membrane-bounded compartments. In all eukaryotic cells intracellular membrane trafficking is critical for a range of important cellular functions including protein secretion, post-translational modifications, cell signalling, cell polarization, and cell maintenance. Defects in membrane trafficking can underline, or even exacerbate, a number of human diseases including cancer, diabetes mellitus, Alzheimer’s, cystic fibrosis, Hermansky-Pudlak syndrome and Congenital Disorders of Glycosylation.
Our research directed towards the understanding of the basic mechanisms of intracellular vesicular trafficking using both yeast and mammalian tissue culture cell model systems. Our lab played a principal role in the discovery of a novel vesicle tethering factors, published more than 50 original papers in high-profile journals, including Journal of Cell Biology, PNAS, Journal of Neuroscience, Molecular Biology of Cell and recent publication in Nature Communications. My current research has been continuously supported by grants from both NSF and NIH.
We have pioneered the functional analysis of the Conserved Oligomeric Golgi (COG), an evolutionarily conserved complex of eight gene products, each of which is critical for the membrane trafficking and protein modifications in the Golgi apparatus. The COG complex interacts with core fusion machinery components including SNAREs, SM proteins, Rabs, coiled-coil tethers and COPI coat to organize specific docking and fusion of transport intermediates with their acceptor membrane. By using state of the art biochemical, genetic and microscopy approaches, we would like to determine how the key components of intracellular membrane trafficking machinery work together to direct efficient protein trafficking in human cells.
Willett R., Ungar D., Lupashin V.V. The Golgi puppet master – COG complex at center stage of membrane trafficking interactions. Histochemistry and Cell Biology 2013, Jul 10. Epub ahead of print
Willett R., Pokrovskaya I., Lupashin V.V. Fluorescent microscopy as a tool to elucidate dysfunction and mislocalization of Golgi glycosyltransferases in COG complex depleted mammalian cells. Methods Mol Biol. 2013 (1022):61-72
Willett R., Kudlyk T., Pokrovskaya I., Schonherr, R., Ungar D., Duden R., Lupashin V.V. COG complexes form spatial landmarks for distinct SNARE complexes. Nature Communications 2013, 4:1553
Kudlyk T., Willett R., Pokrovskaya I., Lupashin V.V . COG6 interacts with a subset of the Golgi SNAREs and is important for the Golgi complex integrity. Traffic 2013;14(2):194-204
Pokrovskaya ID, Szwedo JW, Goodwin A, Lupashina TV, Nagarajan UM, Lupashin VV. Chlamydia trachomatis hijacks intra-Golgi COG complex-dependent vesicle trafficking pathway. Cell Microbiol 2012;14(5):656-668.
Pokrovskaya ID, Willett R, Smith RD, Morelle W, Kudlyk T, Lupashin VV. Conserved oligomeric Golgi complex specifically regulates the maintenance of Golgi glycosylation machinery. Glycobiology 2011;21(12):1554-1569.
Smith RD, Willett R, Kudlyk T, Pokrovskaya I, Paton AW, Paton JC, Lupashin VV. The COG complex, Rab6 and COPI define a novel Golgi retrograde trafficking pathway that is exploited by SubAB toxin. Traffic 2009 Oct;10(10):1502-17
Richardson BC, Smith RD, Ungar D, Nakamura A, Jeffrey PD, Lupashin VV, Hughson FM. Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene. Proc Natl Acad Sci U S A 2009 Aug 11;106(32):13329-34.
Ahmed BA, Bukhari IA, Jeffus BC, Harney JT, Thyparambil S, Ziu E, Fraer M, Rusch NJ, Zimniak P, Lupashin V, Tang D, Kilic F. The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network. PLoS One 2009;4(3):e4730. Epub 2009 Mar 9.
Smith RD, Lupashin VV: Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydr Res 2008, 343(12):2024-2031.
Sun Y, Shestakova A, Hunt L, Sehgal S, Lupashin V, Storrie B: Rab6 regulates both ZW10/RINT-1 and conserved oligomeric Golgi complex-dependent Golgi trafficking and homeostasis. Mol Biol Cell 2007, 18(10):4129-4142.
Shestakova A, Suvorova E, Pavliv O, Khaidakova G, Lupashin V: Interaction of the conserved oligomeric Golgi complex with t-SNARE Syntaxin5a/Sed5 enhances intra-Golgi SNARE complex stability. J Cell Biol 2007, 179(6):1179-1192.