Endophilin Is Required for Synaptic Vesicle Endocytosis by Localizing Synaptojanin

• Published in: Neuron (Cambridge, Mass.) Vol. 40; no. 4; pp. 749 - 762
• Main Authors: Schuske, Kimberly R, Richmond, Janet E, Matthies, Dawn Signor, Davis, Warren S, Runz, Steffen, Rube, Daniel A, van der Bliek, Alexander M, Jorgensen, Erik M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13-11-2003; Elsevier Limited
• Subjects: Acids; Acyltransferases - genetics; Acyltransferases - isolation & purification; Acyltransferases - metabolism; Animals; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - ultrastructure; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - isolation & purification; Caenorhabditis elegans Proteins - metabolism; Cell culture; DNA, Complementary - analysis; DNA, Complementary - genetics; Endocytosis; Endocytosis - genetics; endophilin; Grants; Insects; Microscopy, Electron; Molecular Sequence Data; Mutation; Mutation - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Plasma; Presynaptic Terminals - metabolism; Presynaptic Terminals - ultrastructure; Proteins; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Studies; Synaptic Membranes - genetics; Synaptic Membranes - metabolism; Synaptic Membranes - ultrastructure; Synaptic Transmission - genetics; Synaptic Vesicles - metabolism; Synaptic Vesicles - ultrastructure; synaptojanin
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(03)00667-6

Endophilin is a membrane-associated protein required for endocytosis of synaptic vesicles. Two models have been proposed for endophilin: that it alters lipid composition in order to shape membranes during endocytosis, or that it binds the polyphosphoinositide phosphatase synaptojanin and recruits this phosphatase to membranes. In this study, we demonstrate that the unc-57 gene encodes the Caenorhabditis elegans ortholog of endophilin A. We demonstrate that endophilin is required in C. elegans for synaptic vesicle recycling. Furthermore, the defects observed in endophilin mutants closely resemble those observed in synaptojanin mutants. The electrophysiological phenotype of endophilin and synaptojanin double mutants are virtually identical to the single mutants, demonstrating that endophilin and synaptojanin function in the same pathway. Finally, endophilin is required to stabilize expression of synaptojanin at the synapse. These data suggest that endophilin is an adaptor protein required to localize and stabilize synaptojanin at membranes during synaptic vesicle recycling.