Syntaphilin: a syntaxin-1 clamp that controls SNARE assembly.
Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduces neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibits synaptic transmission. These findings suggest that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis.
Lao
G
G
Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4154, USA.
Scheuss
V
V
Gerwin
C M
CM
Su
Q
Q
Mochida
S
S
Rettig
J
J
Sheng
Z H
ZH
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism*; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism; D050827:Syntaxin 1; D013601:T-Lymphocytes / Q000166:cytology; D014162:Transfection; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger; C494208:SNAP25 protein, human; D050600:SNARE Proteins; C405513:SNPH protein, human; C494212:STX1A protein, human; C494210:Snap25 protein, rat; C494213:Stx1a protein, rat; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins