COLL 41 |
| Sanja Sever, Department of Medicine, Harvard Medical School and Program in Membrane Biology Renal Unit, Department of Medicine, Harvard Medical School and Program in Membrane Biology Renal Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129 |
| Clathrin-coated vesicle formation at the plasma membrane underlies the process of clathrin-mediated endocytosis by which the cell internalizes receptors, transmembrane channels, transporters and extracellular ligands such as hormones, growth factors and nutrients. One of the essential factors required for endocytosis is the GTPase dynamin, whose mechanism of action remains uncertain. Recent evidence suggests that dynamin is a master regulator of endocytosis, using its GTPase cycle to recruit the protein machinery that executes the events underlying endocytosis. This laboratory has now identified Hsc70 and its co-chaperone auxilin as two proteins that specifically interact with dynamin:GTP (Newmyer et al., 2003, Developmental Cell 4:929-940). Hsc70 and auxilin were already known to function during the late stages of endocytosis where they catalyze removal of the clathrin coat from vesicles that have budded. We mapped two domains within auxilin that interact with dynamin, and these domains inhibit endocytosis when overexpressed in HeLa cells or when added in a permeable cell assay. The inhibition is not due to impairment of clathrin uncoating or to altered clathrin distribution in cells. Thus, in addition to its requirement for clathrin uncoating, our results suggest that auxilin also acts during the early steps of clathrin vesicle formation. We propose that dynamin regulates the chaperone machinery to induce controlled conformational changes within the clathrin coat that in turn drive vesicle constriction and fission. |
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Bio-Colloids
2:00 PM-4:30 PM, Sunday, March 28, 2004 Marriott -- Grand Ballroom J, Oral
Division of Colloid and Surface Chemistry |