Article
- The EMBO Journal (2006) 25, 2856 - 2866
- doi:10.1038/sj.emboj.7601165
Published online: 8 June 2006
Subject Category:
Rabphilin regulates SNARE-dependent re-priming of synaptic vesicles for fusion
Ferenc Deák1,2, Ok-Ho Shin1, Jiong Tang1, Phyllis Hanson3,a, Josep Ubach4, Reinhard Jahn3,b, Josep Rizo4, Ege T Kavalali1,5 and Thomas C Südhof1,2,6
- Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA
- Department of Pharmacology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
- Departments of Biochemistry and Pharmacology, UT Southwestern Medical Center, Dallas, TX, USA
- Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX, USA
Correspondence to:
Thomas C Südhof, Center for Basic Neuroscience and HHMI, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd NA4.118, Dallas, TX 75390-9111, USA. Tel.: +1 214 648 1876; Fax: +1 214 648 1979; E-mail: thomas.sudhof@utSouthwestern.edu or Sudhof@UTSouthwestern.edu
aPresent address: Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110-1093, USA
bPresent address: Department of Neurobiology, MPI für biophysikalische Chemie, 37075 Göttingen, Germany
Received 20 May 2005; Accepted 3 May 2006
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.
Keywords:
- exocytosis,
- neurotransmitter release,
- synapse,
- synaptic plasticity,
- synaptobrevin
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