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Originally published In Press as doi:10.1074/jbc.M800738200 on June 4, 2008

J. Biol. Chem., Vol. 283, Issue 30, 20628-20634, July 25, 2008
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Synaptic Vesicle Protein 2 Binds Adenine Nucleotides*

Jia Yao and Sandra M. Bajjalieh1

From the Department of Pharmacology, University of Washington, Seattle, Washington 98195

Synaptic vesicle protein 2 (SV2) is required for normal calcium-regulated secretion of hormones and neurotransmitters. Neurons lacking the two most widely expressed isoforms, SV2A and SV2B, have a reduced readily releasable pool of synaptic vesicles, indicating that SV2 contributes to vesicle priming. The presence of putative ATP-binding sites in SV2 suggested that SV2 might be an ATP-binding protein. To explore this, we examined the binding of the photoaffinity reagent 8-azido-ATP[{gamma}] biotin to purified, recombinant SV2 in the presence and absence of other nucleotides. Our results indicate that SV2A and SV2B bind nucleotides, with the highest affinity for adenine-containing nucleotides. SV2A contains two binding sites located in the cytoplasmic domains preceding the first and seventh transmembrane domains. These results suggest that SV2-mediated vesicle priming could be regulated by adenine nucleotides, which might provide a link between cellular energy levels and regulated secretion.


Received for publication, January 29, 2008 , and in revised form, May 9, 2008.

* This work was supported, in whole or in part, by National Institutes of Health, National Institute of Mental Health Grant R01MH059842 (to S. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Pharmacology, University of Washington, 1959 NE Pacific St., Box 357750, Seattle, WA 98195. Tel.: 206-616-2962; Fax: 206-616-4235; E-mail: bajjalie{at}u.washington.edu.


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