Vladimir Lupashin
Professor
Ph.D., Russian Academy of Science
Office (501) 603-1170
Lab (501) 603-1171

vvlupashin@uams.edu

Our laboratory is interested in understanding the molecular mechanisms responsible for the generation and maintenance of intracellular membrane-bound compartments in the secretory/endocytic pathways of human cells. In all eukaryotic cells, intracellular membrane trafficking is critical for a range of essential cellular functions including protein secretion, post-translational modifications, cell signaling, cell polarization, and cell maintenance. Defects in membrane trafficking can underlie, or exacerbate, a number of human diseases including cancer, diabetes mellitus, Alzheimer’s, cystic fibrosis, Hermansky-Pudlak syndrome and Congenital Disorders of Glycosylation.

Our research is directed towards the understanding of the fundamental mechanisms of intracellular membrane trafficking in health and disease conditions using both mammalian cell and yeast model systems. Our lab has played a principal role in the discovery of novel vesicle tethering factors, and published more than 60 original papers in high-profile journals, including Journal of Cell Biology, PNAS, Journal of Neuroscience, Molecular Biology of Cell, Scientific Reports, Nature Communications and Nature Optics. Our 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 protein complex of eight gene products, each of which is critical for membrane trafficking and protein modifications in the Golgi apparatus. The COG complex interacts with components of the core fusion machinery, including SNAREs, SM proteins, Rabs, coiled-coil tethers and the COPI coat, to organize docking and fusion of transport vesicles with their acceptor membrane. By using state of the art biochemical (in vitro reconstitution), genetic (CRISPR/Cas9 gene editing) and microscopy (superresolution fluorescent, live cell and electron microscopy) approaches, we will further determine how the key components of intracellular membrane trafficking machinery work together to direct efficient protein trafficking in human cells.COG complex regulates retrograde Golgi trafficking

In vivo tethering

The Lupashin laboratory has created knock-outs (KOs) of the COG complex using CRISPR-Cas9 gene editing. The COG KO cells have enlarged endolysosomal compartments (EELCs) that are less mobile than normal lysosomes and have Lamp2 (red) and Rab7a (green) on their membrane. EELCs can uptake cargo from the cell’s surface which has been labeled with the lectin GNL (blue).

The Lupashin laboratory has created knock-outs (KOs) of the COG complex using CRISPR-Cas9 gene editing. The COG KO cells have enlarged endolysosomal compartments (EELCs) that are less mobile than normal lysosomes and have Lamp2 (red) and Rab7a (green) on their membrane. EELCs can uptake cargo from the cell’s surface which has been labeled with the lectin GNL (blue).

 

Representative Publications

Willett R., Bailey Blackburn J., Climer L., Pokrovskaya I., Kudlyk T., Wang W., Lupashin V.V.  COG lobe B sub-complex engages v-SNARE GS15 and functions via regulated interaction with lobe A sub-complex. Scientific Reports 2016; 6; 29139

Bailey Blackburn J., Pokrovskaya I.D., Fisher P., Ungar D., Lupashin V.V. COG Complex Complexities: Detailed characterization of a complete set of HEK293T cells missing individual COG subunits. Front. Cell. Dev. Biol. 2016; 4:23

Siegel N., Lupashin V., Storrie B., Brooker G. High-magnification super-resolution FINCH microscopy using birefringent crystal lens interferometers. Nature Photonics 2016; 10 (12), 802-808

Li Y., Hadden C., Cooper A., Wu H., Lupashin V.V., Mayeux F., Kilic F. Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability. Scientific Reports 2016; 6; 22747

Climer L.K., Dobretsov M., and Lupashin V. Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function. Front Neurosci 2015; 9, 405.

Ha J.Y., Pokrovskaya I.D., Climer L.K., Shimamura G.R., Kudlyk T., Jeffrey P.D., Lupashin V.V., Hughson F.M. Cog5-Cog7 crystal structure reveals interactions essential for the function of a multi-subunit tethering complex. Proc Natl Acad Sci U S A 2014;111(44): 15762-15767.

Zhang Y., Yeruva L., Marinov A., Prantner D., Danciu T., Wyrick ., Lupashin V., Nagarajan U.M. The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN beta during Chlamydia trachomatis infection. Journal of Immunology. 2014, 193(5):2394-2404

Nishimura T., Uchida Y., Yachi R., Kudlyk T., Lupashin V., Inoue T, Yasunori, Taguchi T., Arai H. Oxysterol-binding protein (OSBP) is required for the perinuclear localization of intra-Golgi v-SNAREs. Molecular Biology of the Cell 2013, 24(22):3534-3544

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, 140(3):271-283

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

Miller V., Sharma P., Kudlyk T., Frost L., Rofe A., Watson I., Duden R., Lowe M., Lupashin V.V., Ungar D.  Molecular Insights into Vesicle Tethering at the Golgi by the Conserved Oligomeric Golgi (COG) Complex and the Golgin TATA Element Modulatory Factor (TMF).  Journal of Biological Chemistry 2013, 288(6):4229-4240

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.

Gokhale A, Larimore J, Werner E, So L, Moreno-De-Luca A, Lese-Martin C, Lupashin VV, Smith Y, Faundez V. Quantitative Proteomic and Genetic Analyses of the Schizophrenia Susceptibility Factor Dysbindin Identify Novel Roles of the Biogenesis of Lysosome-Related Organelles Complex 1. J Neurosci 2012;32(11):3697-3711.

 

Complete list of published work in Google Scholar