Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating.
We describe the isolation and characterization of Drosophila synaptojanin (synj) mutants. synj encodes a phosphatidylinositol phosphatase involved in clathrin-mediated endocytosis. We show that Synj is specifically localized to presynaptic terminals and is associated with synaptic vesicles. The electrophysiological and ultrastructural defects observed in synj mutants are strikingly similar to those found in endophilin mutants, and Synj and Endo colocalize and interact biochemically. Moreover, synj; endo double mutant synaptic terminals exhibit properties that are very similar to terminals of each single mutant, and overexpression of Endophilin can partially rescue the functional defects in partial loss-of-function synj mutants. Interestingly, Synj is mislocalized and destabilized at synapses devoid of Endophilin, suggesting that Endophilin recruits and stabilizes Synj on newly formed vesicles to promote vesicle uncoating. Our data also provide further evidence that kiss-and-run is able to maintain neurotransmitter release when synapses are not extensively challenged.
Verstreken
Patrik
P
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Koh
Tong-Wey
TW
Schulze
Karen L
KL
Zhai
R Grace
RG
Hiesinger
P Robin
PR
Zhou
Yi
Y
Mehta
Sunil Q
SQ
Cao
Yu
Y
Roos
Jack
J
Bellen
Hugo J
HJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002966:Clathrin / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004331:Drosophila melanogaster; D004705:Endocytosis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D008561:Membrane Fusion / Q000235:genetics; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002966:Clathrin; D009419:Nerve Tissue Proteins; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases