title: Multiple modes of endophilin-mediated conversion of lipid vesicles into coated tubes: implications for synaptic endocytosis.
abstract: Endophilin A1 is a BAR (Bin/amphiphysin/Rvs) protein abundant in neural synapses that senses and induces membrane curvature, contributing to neck formation in presynaptic endocytic vesicles. To investigate its role in membrane remodeling, we used cryoelectron microscopy to characterize structural changes induced in lipid vesicles by exposure to endophilin. The vesicles convert rapidly to coated tubules whose morphology reflects the local concentration of endophilin. Their diameters and curvature resemble those of synaptic vesicles in situ. Three-dimensional reconstructions of quasicylindrical tubes revealed arrays of BAR dimers, flanked by densities that we equate with amphipathic helices whose folding and membrane insertion were attested by EPR. We also observed the compression of bulbous coated tubes into 70-A-wide cylindrical micelles, which appear to mimic the penultimate (hemi-fission) stage of endocytosis. Our findings suggest that the adaptability of endophilin-lipid interactions underlies dynamic changes of endocytic membranes.
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Mizuno
authors.forename: Christine C
authors.initials: CC
authors.lastname: Jao
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
mesh_terms: D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D004705:Endocytosis; D007091:Image Processing, Computer-Assisted; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D051381:Rats; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D008823:Micelles; D010743:Phospholipids; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase