Impairment of dynamin's GAP domain stimulates receptor-mediated endocytosis.
Dynamin is a GTP-hydrolysing protein that is an essential participant in clathrin-mediated endocytosis by cells. It self-assembles into 'collars' in vitro which also formin 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 self-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 endocytosis is accelerated. The results indicate that dynamin, like other members of the GTPase superfamily, functions as a molecular regulator in receptor-mediated endocytosis, rather than as a force-generating GTPase.
Sever
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Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Muhlberg
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Schmid
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000502:physiology; D006868:Hydrolysis; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011506:Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
D020690:GTPase-Activating Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D034281:Dynamins