双栖小泡蛋白和N-WASP调节肌蛋白组装的相互作用动力学
Amphiphysin 1, an endocytic adaptor concentrated at synapsesthat couples clathrin-mediated endocytosis to dynamin-dependentfission,wasalsoshownto have a regulatory role in actindynamics.Here, we report that amphiphysin 1 interacts with N-WASPand stimulates N-WASP- and Arp2/3-dependent actin polymerization.Both the Src homology 3 and the N-BAR domains arerequiredforthisstimulation.Acidicliposome-triggered,N-WASPdependentactin polymerization is strongly impaired in braincytosol of amphiphysin 1 knock-out mice. FRET-FLIM analysis ofSertoli cells, where endogenously expressed amphiphysin 1 colocalizeswith N-WASP in peripheral ruffles, confirmed theassociation between the two proteins in vivo. This associationundergoes regulation and is enhanced by stimulating phosphatidylserinereceptors on the cell surface with phosphatidylserine-containing liposomes that trigger ruffle formation.These results indicate that actin regulation is a key function ofamphiphysin 1 and that such function cooperates with the endocyticadaptor role and membrane shaping/curvature sensingproperties of the protein during the endocytic reaction.