The Role of Snapin in Neurosecretion:SnapinKnock-Out Mice Exhibit Impaired Calcium-Dependent Exocytosis of Large Dense-Core Vesicles in Chromaffin Cells

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Bibliographische Detailangaben
Zeitschriftentitel:	The Journal of Neuroscience
Personen und Körperschaften:	Tian, Jin-Hua, Wu, Zheng-Xing, Unzicker, Michael, Lu, Li, Cai, Qian, Li, Cuiling, Schirra, Claudia, Matti, Ulf, Stevens, David, Deng, Chuxia, Rettig, Jens, Sheng, Zu-Hang
In:	The Journal of Neuroscience, 25, 2005, 45, S. 10546-10555
Format:	E-Article
Sprache:	Englisch
veröffentlicht:	Society for Neuroscience
Schlagwörter:	General Neuroscience

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Zusammenfassung:	<jats:p>Identification of the molecules that regulate the priming of synaptic vesicles for fusion and the structural coupling of the calcium sensor with the soluble<jats:italic>N</jats:italic>-ethyl maleimide sensitive factor adaptor protein receptor (SNARE)-based fusion machinery is critical for understanding the mechanisms underlying calcium-dependent neurosecretion. Snapin binds to synaptosomal-associated protein 25 kDa (SNAP-25) and enhances the association of the SNARE complex with synaptotagmin. In the present study, we abolished<jats:italic>snapin</jats:italic>expression in mice and functionally evaluated the role of Snapin in neuroexocytosis. We found that the association of synaptotagmin-1 with SNAP-25 in brain homogenates of<jats:italic>snapin</jats:italic>mutant mice is impaired. Consequently, the absence of Snapin in embryonic chromaffin cells leads to a significant reduction of calcium-dependent exocytosis resulting from a decreased number of vesicles in releasable pools. Overexpression of Snapin fully rescued this inhibitory effect in the mutant cells. Furthermore, Snapin is relatively enriched in the purified large dense-core vesicles of chromaffin cells and associated with synaptotagmin-1. Thus, our biochemical and electrophysiological studies using<jats:italic>snapin</jats:italic>knock-out mice demonstrate that Snapin plays a critical role in modulating neurosecretion by stabilizing the release-ready vesicles.</jats:p>
Umfang:	10546-10555
ISSN:	0270-6474 1529-2401
DOI:	10.1523/jneurosci.3275-05.2005