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

Nature. 1999 Apr 8;398(6727):481-6. doi: 10.1038/19024.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cell Line
  • Cloning, Molecular
  • Dynamins
  • Endocytosis / physiology*
  • GTP Phosphohydrolases / biosynthesis
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • GTPase-Activating Proteins
  • Guanosine Triphosphate / physiology
  • Hydrolysis
  • Molecular Sequence Data
  • Mutagenesis
  • Proteins / physiology*
  • Receptors, Cell Surface / physiology*
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid

Substances

  • GTPase-Activating Proteins
  • Proteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • Dynamins