Molecular Biology of the Cell

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print December 12, 2007
Mol. Biol. Cell 10.1091/mbc.E07-07-0662

A more recent version of this article appeared on February 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-07-0662v1
19/2/722    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arunachalam, L.
Right arrow Articles by Sugita, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arunachalam, L.
Right arrow Articles by Sugita, S.

Submitted on July 13, 2007
Revised on October 31, 2007
Accepted on November 29, 2007

Munc18-1 Is Critical for Plasma Membrane Localization of Syntaxin1 but Not of SNAP-25 in PC12 Cells

Lakshmanan Arunachalam,*{dagger} Liping Han,*{dagger} Nardos G. Tassew,{ddagger} Yu He,{dagger}{sect} Li Wang,* Li Xie,{dagger}{sect} Yoshihito Fujita,* Edwin Kwan,{dagger}{sect} Bazbek Davletov,|| Philippe P. Monnier,{dagger}{ddagger} Herbert Y. Gaisano,*{dagger}{sect} and Shuzo Sugita*{dagger}

*Division of Fundamental Neurobiology and {ddagger}Division of Genetics and Development, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada; Departments of {dagger}Physiology and {sect}Medicine, Faculty of Medicine, University of Toronto, Ontario, M5S 1A8, Canada; ||MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

Monitoring Editor: Benjamin Glick

Although Munc18–1 was originally identified as a syntaxin1 interacting protein, the physiological significance of this interaction remains unclear. In fact, recent studies of Munc18–1 mutants have suggested that Munc18–1 plays a critical role for docking of secretory vesicles, independent of syntaxin1 regulation. Here we investigated the role of Munc18–1 in syntaxin1 localization by generating stable neuroendocrine cell lines in which Munc18–1 was strongly down-regulated. In these cells, the secretion capability, as well as the docking of dense-core vesicles, was significantly reduced. More importantly, not only was the expression level of syntaxin1 reduced, but the localization of syntaxin1 at the plasma membrane was also severely perturbed. The mislocalized syntaxin1 resided primarily in the perinuclear region of the cells, in which it was highly colocalized with Secretogranin II, a marker protein for dense-core vesicles. In contrast, the expression level and the plasma membrane localization of SNAP-25 were not affected. Furthermore, the syntaxin1 localization and the secretion capability were restored upon transfection-mediated reintroduction of Munc18–1. Our results indicate that endogenous Munc18–1 plays a critical role for the plasma membrane localization of syntaxin1 in neuroendocrine cells, and therefore necessitate the interpretation of Munc18–1 mutant phenotypes to be in terms of mislocalized syntaxin1.

Address correspondence to: Shuzo Sugita (ssugita{at}uhnres.utoronto.ca)




This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
M. E. Graham, M. R. Edwards, L. Holden-Dye, A. Morgan, R. D. Burgoyne, and J. W. Barclay
UNC-18 Modulates Ethanol Sensitivity in Caenorhabditis elegans
Mol. Biol. Cell, January 1, 2009; 20(1): 43 - 55.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
T. L. Rodkey, S. Liu, M. Barry, and J. A. McNew
Munc18a Scaffolds SNARE Assembly to Promote Membrane Fusion
Mol. Biol. Cell, December 1, 2008; 19(12): 5422 - 5434.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.