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 dyn amin, 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 endop hilin-I-mediated SLMV formation requires the transfer of the unsaturated fa tty acid arachidonate to lysophosphatidic acid, converting it to phosphatid ic acid. A deletion mutant lacking the SH3 domain through which endophilin I interacts with dynamin still exhibits LPAAT activity but no longer mediat es SLMV formation. These results indicate that endophilin I may induce nega tive membrane curvature by converting an inverted-cone-shaped lipid to a co ne-shaped lipid in the cytoplasmic leaflet of the bilayer. We propose that, through this action, endophilin I works with dynamin to mediate synaptic v esicle invagination from the plasma membrane and fission.