Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis

Dynamin is a GTP-hydrolysing protein that is an essential participant in cl athrin-mediated endocytosis by cells. It self-assembles into 'collars' in v itro which also form in vivo at the necks of invaginated coated pits. This self-assembly stimulates dynamin's GTPase activity and it has been proposed that dynamin hydrolyses GTP in order to generate the force needed to sever vesicles from the plasma membrane. A mechanism is now described in which s elf-assembly of dynamin is coordinated by a domain of dynamin with a GTPase -activating function. Unexpectedly, when dynamin mutants defective in self- assembly-stimulated GTPase activity are overexpressed, receptor-mediated en docytosis is accelerated. The results indicate that dynamin, like other mem bers of the GTPase superfamily, functions as a molecular regulator in recep tor-mediated endocytosis, rather than as a force-generating GTPase.