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 Vladimir 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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