SNAP-29: A general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission
- *Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4154; and †Department of Physiology, Tokyo Medical University, Tokyo 160-8402, Japan
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Communicated by William A. Catterall, University of Washington School of Medicine, Seattle, WA (received for review May 10, 2001)
Abstract
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 α-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.
Footnotes
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↵ ‡ To whom reprint requests should be addressed. E-mail: shengz{at}ninds.nih.gov.
- Abbreviations:
- NSF,
- N-ethylmaleimide-sensitive factor;
- SNAP,
- soluble NSF attachment protein;
- SNARE,
- SNAP receptor;
- SCGN,
- superior cervical ganglion neuron;
- GST,
- glutathione S-transferase;
- EPSP,
- excitatory postsynaptic potential
- Copyright © 2001, The National Academy of Sciences
