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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 21, 2004, 24(16):3964-3973; doi:10.1523/JNEUROSCI.5259-03.2004

This Article Full Text Full Text (PDF) 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 ISI 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 ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Babcock, M. Articles by Pallanck, L. Search for Related Content PubMed PubMed Citation Articles by Babcock, M. Articles by Pallanck, L.

 Previous Article  |  Next Article 

Cellular/Molecular
Genetic Analysis of Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Function in Drosophila Reveals Positive and Negative Secretory Roles

Michael Babcock, Greg T. Macleod, Jennifer Leither, and Leo Pallanck

Department of Genome Sciences, University of Washington, Seattle, Washington 98195

The N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP) are cytosolic factors that promote vesicle fusion with a target membrane in both the constitutive and regulated secretory pathways. NSF and SNAP are thought to function by catalyzing the disassembly of a SNAP receptor (SNARE) complex consisting of membrane proteins of the secretory vesicle and target membrane. Although studies of NSF function have provided strong support for this model, the precise biochemical role of SNAP remains controversial. To further explore the function of SNAP, we have used mutational and transgenic approaches in Drosophila to investigate the effect of altered SNAP dosage on neurotransmitter release and SNARE complex metabolism. Our results indicate that reduced SNAP activity results in diminished neurotransmitter release and accumulation of a neural SNARE complex. Increased SNAP dosage results in defective synapse formation and a variety of tissue morphological defects without detectably altering the abundance of neural SNARE complexes. The SNAP overexpression phenotypes are enhanced by mutations in other secretory components and are at least partially overcome by co-overexpression of NSF, suggesting that these phenotypes derive from a specific perturbation of the secretory pathway. Our results indicate that SNAP promotes neurotransmitter release and SNARE complex disassembly but inhibits secretion when present at high abundance relative to NSF.

Key words: Drosophila; mutant; secretion; synapse; SNAP; NSF; SNARE

---

Received Nov 3, 2003; revised March 8, 2004; accepted March 9, 2004.

This article has been cited by other articles:

				M. Barszczewski, J. J. Chua, A. Stein, U. Winter, R. Heintzmann, F. E. Zilly, D. Fasshauer, T. Lang, and R. Jahn A Novel Site of Action for {alpha}-SNAP in the SNARE Conformational Cycle Controlling Membrane Fusion Mol. Biol. Cell, March 1, 2008; 19(3): 776 - 784. [Abstract] [Full Text] [PDF]

				A. Simonsen, R. C. Cumming, K. Lindmo, V. Galaviz, S. Cheng, T. E. Rusten, and K. D. Finley Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport With Decreased Life Span and Altered Ubiquitinated-Protein Profiles Genetics, June 1, 2007; 176(2): 1283 - 1297. [Abstract] [Full Text] [PDF]

				U. Acharya, M. B. Edwards, R. A. Jorquera, H. Silva, K. Nagashima, P. Labarca, and J. K. Acharya Drosophila melanogaster Scramblases modulate synaptic transmission. J. Cell Biol., April 10, 2006; 173(1): 69 - 82. [Abstract] [Full Text] [PDF]

				N. Haines and K. D. Irvine Functional analysis of Drosophila {beta}1,4-N-acetlygalactosaminyltransferases Glycobiology, April 1, 2005; 15(4): 335 - 346. [Abstract] [Full Text] [PDF]

				C.N. Tomes, G.A. De Blas, M.A. Michaut, E.V. Farre, O. Cherhitin, P.E. Visconti, and L.S. Mayorga {alpha}-SNAP and NSF are required in a priming step during the human sperm acrosome reaction Mol. Hum. Reprod., January 1, 2005; 11(1): 43 - 51. [Abstract] [Full Text] [PDF]

				T. Galli and V. Haucke Cycling of Synaptic Vesicles: How Far? How Fast! Sci. Signal., December 21, 2004; 2004(264): re19 - re19. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help