Dynamin Is Membrane-Active:  Lipid Insertion Is Induced by Phosphoinositides and Phosphatidic Acid

• Published in: Biochemistry (Easton) Vol. 39; no. 40; pp. 12485 - 12493
• Main Authors: Burger, Koert N. J, Demel, Rudy A, Schmid, Sandra L, de Kruijff, Ben
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.10.2000
• Subjects: Animals; Binding Sites; Blood Platelets - chemistry; Blood Proteins - chemistry; Cattle; Dynamins; Endocytosis; Genetic Vectors; GTP Phosphohydrolases - chemistry; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; 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
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi000971r

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.