title: Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding.
abstract: DYNAMIN, a 100K member of the GTPase superfamily, is the mammalian homologue of the Drosophila shibire gene product. Mutations in shibire cause a defect in endocytosis leading to accumulation of coated pits and deep invaginations at the plasma membrane of all tissues examined. Similarly, invaginated coated pits accumulate in mammalian cells overexpressing dominant-negative mutants of dynamin, establishing that dynamin is required for the formation of 'constricted' coated pits and for coated vesicle budding. Whether dynamin functions in the classic GTPase mode as a molecular switch to regulate events leading to coated vesicle budding or instead actively participates as a mechanochemical enzyme driving coated vesicle formation is unclear. Here we show that dynamin spontaneously self-assembles into rings and stacks of interconnected rings, comparable in dimension to the 'collars' observed at the necks of invaginated coated pits that accumulate at synaptic terminals in shibire flies. We propose that invaginated coated pits become constricted by the assembly of dynamin into rings around their necks. A concerted conformational change would then close the rings and pinch off the budding coated vesicles.
authors.affiliation: Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037.
authors.forename: J E
authors.initials: JE
authors.lastname: Hinshaw
authors.forename: S L
authors.initials: SL
authors.lastname: Schmid
mesh_terms: D000818:Animals; D002460:Cell Line; D002966:Clathrin / Q000502:physiology; D018699:Coated Vesicles / Q000502:physiology*; D029721:Drosophila Proteins; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D011392:Proline / Q000502:physiology; D011994:Recombinant Proteins; D018411:Spodoptera
chemical_list: D002966:Clathrin; D029721:Drosophila Proteins; D011994:Recombinant Proteins; D011392:Proline; D020558:GTP Phosphohydrolases; D034281:Dynamins; C439628:shi protein, Drosophila