Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion

Ferenc Deák, Ok Ho Shin, Jiong Tang, Phyllis Hanson, Josep Ubach, Reinhard Jahn, Jose Rizo-Rey, Ege T Kavalali, Thomas C. Südhof

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

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 C2 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.

Original languageEnglish (US)
Pages (from-to)2856-2866
Number of pages11
JournalEMBO Journal
Volume25
Issue number12
DOIs
StatePublished - Jun 21 2006

Keywords

  • Exocytosis
  • Neurotransmitter release
  • Synapse
  • Synaptic plasticity
  • Synaptobrevin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Deák, F., Shin, O. H., Tang, J., Hanson, P., Ubach, J., Jahn, R., Rizo-Rey, J., Kavalali, E. T., & Südhof, T. C. (2006). Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion. EMBO Journal, 25(12), 2856-2866. https://doi.org/10.1038/sj.emboj.7601165