Dynamin is membrane-active: lipid insertion is induced by phosphoinositides and phosphatidic acid

Biochemistry. 2000 Oct 10;39(40):12485-93. doi: 10.1021/bi000971r.

Abstract

Dynamin is a large GTPase involved in the regulation of membrane constriction and fission during receptor-mediated endocytosis. Dynamin contains a pleckstrin-homology domain which is essential for endocytosis and which binds to anionic phospholipids. Here, we show for the first time that dynamin is a membrane-active molecule capable of penetrating into the acyl chain region of membrane lipids. Lipid penetration is strongly stimulated by phosphatidic acid (PA), phosphatidylinositol 4-phosphate, and phosphatidylinositol 4, 5-bisphosphate. Though binding is more efficient in the presence of the phosphoinositides, a much larger part of the dynamin molecule penetrates into PA-containing mixed-lipid systems. Thus, local lipid metabolism will dramatically influence dynamin-lipid interactions, and dynamin-lipid interactions are likely to play an important role in dynamin-dependent endocytosis. Our data suggest that dynamin is directly involved in membrane destabilization, a prerequisite to membrane fission.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Blood Platelets / chemistry
  • Blood Proteins / chemistry
  • Cattle
  • Dynamins
  • Endocytosis
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Genetic Vectors
  • Humans
  • Intracellular Membranes / chemistry
  • Intracellular Membranes / metabolism*
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism*
  • Microtubules / chemistry
  • Microtubules / metabolism
  • Phosphatidic Acids / chemistry*
  • Phosphatidylinositols / chemistry*
  • Phosphatidylserines / chemistry
  • Phosphoproteins / chemistry
  • Protein Structure, Tertiary / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Spodoptera / genetics

Substances

  • Blood Proteins
  • Membrane Lipids
  • Phosphatidic Acids
  • Phosphatidylinositols
  • Phosphatidylserines
  • Phosphoproteins
  • Recombinant Proteins
  • platelet protein P47
  • 1,2-dioleoylphosphatidylserine
  • GTP Phosphohydrolases
  • Dynamins