Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid.
Endophilin I is a presynaptic protein of unknown function that binds to dynamin, a GTPase that is implicated in endocytosis and recycling of synaptic vesicles. Here we show that endophilin I is essential for the formation of synaptic-like microvesicles (SLMVs) from the plasma membrane. Endophilin I exhibits lysophosphatidic acid acyl transferase (LPAAT) activity, and endophilin-I-mediated SLMV formation requires the transfer of the unsaturated fatty acid arachidonate to lysophosphatidic acid, converting it to phosphatidic acid. A deletion mutant lacking the SH3 domain through which endophilin I interacts with dynamin still exhibits LPAAT activity but no longer mediates SLMV formation. These results indicate that endophilin I may induce negative membrane curvature by converting an inverted-cone-shaped lipid to a cone-shaped lipid in the cytoplasmic leaflet of the bilayer. We propose that, through this action, endophilin I works with dynamin to mediate synaptic vesicle invagination from the plasma membrane and fission.
Schmidt
A
A
Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Wolde
M
M
Thiele
C
C
Fest
W
W
Kratzin
H
H
Podtelejnikov
A V
AV
Witke
W
W
Huttner
W B
WB
Söling
H D
HD
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D063065:Organophosphonates; D016716:PC12 Cells; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000502:physiology*; D018909:src Homology Domains / Q000502:physiology
D000214:Acyl Coenzyme A; D048868:Adaptor Proteins, Signal Transducing; D001095:Arachidonic Acids; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D008563:Membrane Lipids; D063065:Organophosphonates; D011993:Recombinant Fusion Proteins; C107640:SH3GL2 protein, human; C498434:Sh3gl2 protein, mouse; C104810:methyl arachidonylfluorophosphonate; D016718:Arachidonic Acid; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D010741:Phospholipases A