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Rabphilin regulates SNARE‐dependent re‐priming of synaptic vesicles for fusion
Author(s) -
Deák Ferenc,
Shin OkHo,
Tang Jiong,
Hanson Phyllis,
Ubach Josep,
Jahn Reinhard,
Rizo Josep,
Kavalali Ege T,
Südhof Thomas C
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601165
Subject(s) - synaptic vesicle , synaptobrevin , vesicle fusion , microbiology and biotechnology , snap25 , snare complex , biology , exocytosis , synaptotagmin 1 , vesicle , chemistry , biochemistry , secretion , membrane
Synaptic vesicle fusion is catalyzed by assembly of synaptic SNARE complexes, and is regulated by the synaptic vesicle GTP‐binding protein Rab3 that binds to RIM and to rabphilin. RIM is a known physiological regulator of fusion, but the role of rabphilin remains obscure. We now show that rabphilin regulates recovery of synaptic vesicles from use‐dependent depression, probably by a direct interaction with the SNARE protein SNAP‐25. Deletion of rabphilin dramatically accelerates recovery of depressed synaptic responses; this phenotype is rescued by viral expression of wild‐type rabphilin, but not of mutant rabphilin lacking the second rabphilin C 2 domain that binds to SNAP‐25. Moreover, deletion of rabphilin also increases the size of synaptic responses in synapses lacking the vesicular SNARE protein synaptobrevin in which synaptic responses are severely depressed. Our data suggest that binding of rabphilin to SNAP‐25 regulates exocytosis of synaptic vesicles after the readily releasable pool has either been physiologically exhausted by use‐dependent depression, or has been artificially depleted by deletion of synaptobrevin.