title: Dynamin, a GTPase involved in the initial stages of endocytosis.
abstract: Dynamin is a high molecular mass (100 kDa) GTPase which binds to and co-purifies with microtubules. Molecular cloning of rat brain dynamin has revealed the three well-established consensus sequence elements for GTP binding within the N-terminal third of the protein, as well as sequence similarity within this region to the interferon-inducible antiviral Mx proteins, the product of the yeast membrane sorting gene VPS1, and the product of the yeast mitochondrial replication gene MGM1. More extensive sequence similarity between rat dynamin and the product of the Drosophila gene shibire, which is involved in endocytosis, has also been found. In in vitro assays microtubules strongly stimulate the dynamin GTPase. This effect can be reversed by removal of the dynamin C-terminus using papain, which abolishes microtubule binding. Overexpression of mutant forms of dynamin in vivo using Cos-7 cells inhibits transferrin uptake and alters the distribution of clathrin and of alpha-adaptin, but not gamma-adaptin. Deletion of the C-terminus of mutant forms of dynamin abolishes these effects. Together these results suggest a critical role for dynamin in the early stages of endocytosis. It is uncertain whether microtubules interact with dynamin in vivo or whether the in vitro effects of microtubules mimic the effects of other regulatory elements in vivo.
authors.affiliation: Cell Biology Group, Worcester Foundation for Experimental Biology, Shrewsbury, MA.
authors.forename: R B
authors.initials: RB
authors.lastname: Vallee
authors.forename: J S
authors.initials: JS
authors.lastname: Herskovits
authors.forename: J G
authors.initials: JG
authors.lastname: Aghajanian
authors.forename: C C
authors.initials: CC
authors.lastname: Burgess
authors.forename: H S
authors.initials: HS
authors.lastname: Shpetner
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins; D034281:Dynamins; D004705:Endocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D020558:GTP Phosphohydrolases; D034281:Dynamins; C439628:shi protein, Drosophila