SNAP-29: a general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission.
Using the yeast two-hybrid system with syntaxin-1A as bait, we isolated soluble NSF attachment protein (SNAP)-29 from a human brain cDNA library. Synaptosomal fractionation and immunocytochemical staining of hippocampal neurons in culture showed that SNAP-29 is present at synapses and is predominantly associated with synaptic vesicles. The interaction of SNAP-29 with syntaxin-1 was further confirmed with immunoprecipitation analysis. Binding competition studies with SNAP-29 demonstrated that it could compete with alpha-SNAP for binding to synaptic SNAP receptors (SNAREs) and consequently inhibit disassembly of the SNARE complex. Introduction of SNAP-29 into presynaptic superior cervical ganglion neurons in culture significantly inhibited synaptic transmission in an activity-dependent manner. Although SNAP-29 has been suggested to be a general SNARE component in membrane trafficking, our findings suggest that it may function as a regulator of SNARE complex disassembly and modulate the process of postfusion recycling of the SNARE components.
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Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4154, USA.
Mochida
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S
Tian
J H
JH
Mehta
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R
Sheng
Z H
ZH
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013347:Subcellular Fractions; D009435:Synaptic Transmission / Q000502:physiology*; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; D050600:SNARE Proteins; C494212:STX1A protein, human; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins