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lupashin.jpgVladimir V. Lupashin
Associate Professor
Ph.D., Russian Academy of Sciences
Office: (501) 603-1170
Lab: (501) 603-1171
Email: vvlupashin@uams.edu

Our laboratory is interested in understanding the molecular mechanisms responsible for the generation and maintenance of intra-cellular membrane-bounded compartments. Specifically, we study the mechanisms and machinery that maintain the high degree of specificity inherent in transport vesicle docking in the secretory pathway. We are also interested in the mechanism of retention and retrieval of integral membrane proteins in different sub-compartments of the Golgi apparatus.

Golgi vesicle tethering factors were the major focus of our recent research. We have discovered and characterize the evolutionarily Conserved Oligomeric Golgi (COG) complex that plays a major role on the intra-Golgi retrograde membrane trafficking. We have shown that the COG complex interacts with SNAREs, Rab-GTP and the COPI vesicle coat. Cog3p knock-down in Hela cells is accompanied by accumulation of COG complex dependent (CCD) vesicles carrying v-SNAREs, cis-Golgi glycoprotein GPP130 and cis/medial Golgi glycosylation enzymes. A prolonged block in CCD vesicles tethering is accompanied by extensive fragmentation of the Golgi ribbon. Fragmented Golgi membranes maintained their juxtanuclear localization, cisternal organization and are competent for the anterograde trafficking of VSVG protein to the plasma membrane. In a contrast, Cog3p knock-down resulted in inhibition of retrograde trafficking of the Shiga toxin. We are currently characterizing the complex further through biochemical, molecular genetic and cell biological methods.
By using a number of different approaches in both mammalian and yeast systems we hope to shed new light into the vesicular transport mechanism of eukaryotic cells.

Dr. Lupashin's Laboratory Homepage

Representative Publications

Shestakova A., Suvorova E., Pavliv O., Khaidakova G., Lupashin V.V. (2007). Interaction of the Conserved Oligomeric Golgi complex with t-SNARE Syntaxin5a/Sed5 enhances intra-Golgi SNARE complex stability. Journal of Cell Biology, Accepted for publication.

Sun Y., Shestakova A., Hunt L., Sehgal S., Lupashin V.V. Storrie B. 2007. Rab6 regulates both of ZW10/RINT1 and COG complex dependent Golgi trafficking and homeostasis.  Molecular Biology of the Cell, Aug 15

 Ng B., Kranz C., Hagebeuk E., Duran M., Abeling N., Wuyts B., Ungar D., Lupashin V.V , Hartdorff C., Poll-The B., Freeze H. 2007, Molecular and Clinical Characterization of a Moroccan Cog7-Deficient Patient. Molecular Genetics and Metabolism, 91: 201-204.

 Kranz C., Ng B., Sun., Sharma V., Eklund E., Miura Y., Ungar D., Lupashin V.V , Winkel D., Cippolo J., Costello C., Loh E., Hong W., Freeze H. 2007, COG8 deficiency causes new Congenital Disorder of Glycosylation type IIh. Human Molecular Genetics, 16: 731-741.

 Shestakova A., Zolov S., Lupashin V.V.  COG complex-mediated recycling of Golgi glycosyltransferases is essential for normal protein glycosylation. 2006. Traffic, 7:191-204

 Sztul E. and Lupashin V.V.  Role of Tethering factors in Secretory membrane traffic. 2006, Invited Review. American Journal of Physiology –Cell Physiology. 290:C11-26

 Zolov S. and Lupashin V. V. COG3p depletion blocks vesicle-mediated Golgi retrograde trafficking in HeLa cells. 2005. Journal of Cell Biology, 168: 747-759

Link to Dr. Lupashin at PubMed

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