Mechanism of membrane trafficking in the ER-Golgi shuttle
Our laboratory is studying mechanisms of vesicular trafficking of proteins among organelles of the early secretory system (the ER, ERGIC and the Golgi apparatus). In this system vesicle budding is initiated upon activation of a small G protein, followed by the recruitment of a coat protein complex. The G proteins, in turn, are regulated by an array of exchange factors and GTPase-activating proteins (GAPs). Focusing on the COPI system which mediates retrograde Golgi to ER transport, our studies are aimed at understanding the precise role of GTP binding and hydrolysis in vesicle budding and consumption, determining the mode of interaction between the components of the system, and defining which sub-compartment (Golgi/ERGIC) mediates the sorting of membrane and soluble cargo for retrograde transport.
In our studies, we have been collaborating with the group of Bruno Antonny from CNRS Valbonne, France and of Felix Wieland from the Biozentrum, University of Heidelberg, Germany.
• Distinct role of subcomplexes of the COPI coat in the regulation of ArfGAP2 activity. Pevzner I, Strating J, Lifshitz L, Parnis A, Glaser F, Herrmann A, Brügger B, Wieland F, Cassel D.Traffic 13:849-856 (2012).
• ArfGAP1 interacts with coat proteins through tryptophan-based motifs. Rawet M, Levi-Tal S, Szafer-Glusman E, Parnis A, Cassel D. Biochem. Biophys. Res. Commun 394:553–557 (2010).
• Discrete determinants in ArfGAP2/3 conferring Golgi localization and regulation by the COPI coat. Kliouchnikov L, Bigay J, Mesmin B, Parnis A, Rawet M, Cassel D. Mol. Biol. Cell 20:859-869 (2009).
• The COPI system: molecular mechanisms and function. Beck R, Rawet M, Wieland FT, Cassel D. FEBS Lett. 583:2701-9 (2009).
• Topology of amphipathic motifs mediating Golgi localization in ArfGAP1 and its splice isoforms. Levi S, Rawet M, Kliouchnikov L, Parnis A, and Cassel D. J. Biol. Chem. 283:8564-72 (2008).