title: Dynamin is membrane-active: lipid insertion is induced by phosphoinositides and phosphatidic acid.
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.
authors.affiliation: Department of Biochemistry of Membranes, Centre for Biomembranes and Lipid Enzymology, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. K.N.J.Burger@bio.uu.nl
authors.forename: K N
authors.initials: KN
authors.lastname: Burger
authors.forename: R A
authors.initials: RA
authors.lastname: Demel
authors.forename: S L
authors.initials: SL
authors.lastname: Schmid
authors.forename: B
authors.initials: B
authors.lastname: de Kruijff
mesh_terms: D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry; D002417:Cattle; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D010712:Phosphatidic Acids / Q000737:chemistry*; D010716:Phosphatidylinositols / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry; D010750:Phosphoproteins / Q000737:chemistry; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018411:Spodoptera / Q000235:genetics
chemical_list: D001798:Blood Proteins; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010750:Phosphoproteins; D011994:Recombinant Proteins; C039077:platelet protein P47; C042511:1,2-dioleoylphosphatidylserine; D020558:GTP Phosphohydrolases; D034281:Dynamins