Endophilin is required for synaptic vesicle endocytosis by localizing synaptojanin.
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.
Schuske
Kimberly R
KR
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112, USA.
Richmond
Janet E
JE
Matthies
Dawn Signor
DS
Davis
Warren S
WS
Runz
Steffen
S
Rube
Daniel A
DA
van der Bliek
Alexander M
AM
Jorgensen
Erik M
EM
D000217:Acyltransferases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D004705:Endocytosis / Q000235:genetics*; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases