QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 9, 2005, 25(45):10546-10555; doi:10.1523/JNEUROSCI.3275-05.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Tian, J.-H. Articles by Sheng, Z.-H. Search for Related Content PubMed PubMed Citation Articles by Tian, J.-H. Articles by Sheng, Z.-H.

 Previous Article  |  Next Article 

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

Jin-Hua Tian,^1 * Zheng-Xing Wu,^2 * Michael Unzicker,² Li Lu,¹ Qian Cai,¹ Cuiling Li,³ Claudia Schirra,² Ulf Matti,² David Stevens,² Chuxia Deng,³ Jens Rettig,² and Zu-Hang Sheng¹

¹Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, ²Physiologisches Institut, Universitaet des Saarlandes, 66424 Homburg/Saar, Germany, and ³Mammalian Genetics Section, Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892

Identification of the molecules that regulate the priming of synaptic vesicles for fusion and the structural coupling of the calcium sensor with the soluble N-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 snapin 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 snapin 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 snapin knock-out mice demonstrate that Snapin plays a critical role in modulating neurosecretion by stabilizing the release-ready vesicles.

Key words: exocytosis; neurosecretion; SNARE proteins; synaptic vesicle release; chromaffin cell; catecholamine

---

Received Aug 4, 2005; revised September 26, 2005; accepted September 29, 2005.

This article has been cited by other articles:

				X.-W. Chen, Y.-Q. Feng, C.-J. Hao, X.-L. Guo, X. He, Z.-Y. Zhou, N. Guo, H.-P. Huang, W. Xiong, H. Zheng, et al. DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release J. Cell Biol., October 20, 2008; 181(5): 791 - 801. [Abstract] [Full Text] [PDF]

				G. Nagy, I. Milosevic, R. Mohrmann, K. Wiederhold, A. M. Walter, and J. B. Sorensen The SNAP-25 Linker as an Adaptation Toward Fast Exocytosis Mol. Biol. Cell, September 1, 2008; 19(9): 3769 - 3781. [Abstract] [Full Text] [PDF]

				A. Granata, R. Watson, L. M. Collinson, G. Schiavo, and T. T. Warner The Dystonia-associated Protein TorsinA Modulates Synaptic Vesicle Recycling J. Biol. Chem., March 21, 2008; 283(12): 7568 - 7579. [Abstract] [Full Text] [PDF]

				Y. Bao, J. A. Lopez, D. E. James, and W. Hunziker Snapin Interacts with the Exo70 Subunit of the Exocyst and Modulates GLUT4 Trafficking J. Biol. Chem., January 4, 2008; 283(1): 324 - 331. [Abstract] [Full Text] [PDF]

				F. Suzuki, S. Morishima, T. Tanaka, and I. Muramatsu Snapin, a New Regulator of Receptor Signaling, Augments {alpha}1A-Adrenoceptor-operated Calcium Influx through TRPC6 J. Biol. Chem., October 5, 2007; 282(40): 29563 - 29573. [Abstract] [Full Text] [PDF]

				K. Newell-Litwa, E. Seong, M. Burmeister, and V. Faundez Neuronal and non-neuronal functions of the AP-3 sorting machinery J. Cell Sci., February 15, 2007; 120(4): 531 - 541. [Abstract] [Full Text] [PDF]

				K. Talbot, D.-S. Cho, W.-Y. Ong, M. A. Benson, L.-Y. Han, H. A. Kazi, J. Kamins, C.-G. Hahn, D. J. Blake, and S. E. Arnold Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin Hum. Mol. Genet., October 15, 2006; 15(20): 3041 - 3054. [Abstract] [Full Text] [PDF]

				G. Salazar, B. Craige, M. L. Styers, K. A. Newell-Litwa, M. M. Doucette, B. H. Wainer, J. M. Falcon-Perez, E. C. Dell'Angelica, A. A. Peden, E. Werner, et al. BLOC-1 Complex Deficiency Alters the Targeting of Adaptor Protein Complex-3 Cargoes Mol. Biol. Cell, September 1, 2006; 17(9): 4014 - 4026. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help