Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid

Nature. 1999 Sep 9;401(6749):133-41. doi: 10.1038/43613.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Acyltransferases / metabolism
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Arachidonic Acid / metabolism*
  • Arachidonic Acids / pharmacology
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cattle
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Cell Membrane / physiology*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Lysophospholipids / metabolism*
  • Membrane Fusion
  • Membrane Lipids / chemistry
  • Membrane Lipids / physiology*
  • Mice
  • Models, Biological
  • Molecular Conformation
  • Molecular Sequence Data
  • Organophosphonates
  • PC12 Cells
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / metabolism
  • Phosphorylation
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Vesicles / physiology*
  • src Homology Domains / physiology

Substances

  • Acyl Coenzyme A
  • Adaptor Proteins, Signal Transducing
  • Arachidonic Acids
  • Carrier Proteins
  • Enzyme Inhibitors
  • Lysophospholipids
  • Membrane Lipids
  • Organophosphonates
  • Recombinant Fusion Proteins
  • SH3GL2 protein, human
  • Sh3gl2 protein, mouse
  • methyl arachidonylfluorophosphonate
  • Arachidonic Acid
  • Acyltransferases
  • 2-acylglycerophosphate acyltransferase
  • Phospholipases A

Associated data

  • GENBANK/AF009603
  • GENBANK/Q62420
  • GENBANK/Q99962