Molecular Biology of the Cell click for CBE Life Science Education Page

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


     

Originally published as MBC in Press, 10.1091/mbc.E08-08-0872 on January 14, 2009

Vol. 20, Issue 5, 1269-1279, March 1, 2009

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E08-08-0872v1
20/5/1269    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 Shifrin, Y.
Right arrow Articles by McCulloch, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shifrin, Y.
Right arrow Articles by McCulloch, C. A.

The Role of FilGAP-Filamin A Interactions in Mechanoprotection

Yulia Shifrin*, Pamela D. Arora*, Yasutaka Ohta{dagger}, David A. Calderwood{ddagger}, and Christopher A. McCulloch*

*CIHR Group in Matrix Dynamics, University of Toronto, Toronto, Ontario M5S 3E2, Canada; {dagger}Department of Biosciences, School of Science, Kitasato University, Sagamihara Kanagawa 228-8555, Japan; and {ddagger}Department of Pharmacology and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, New Haven, CT 06520

Submitted August 26, 2008; Revised December 19, 2008; Accepted January 6, 2009
Monitoring Editor: Yu-Li Wang

InCytes from MBC

Cells in mechanically active environments are subjected to high-amplitude exogenous forces that can lead to cell death. Filamin A (FLNa) may protect cells from mechanically induced death by mechanisms that are not yet defined. We found that mechanical forces applied through integrins enhanced Rac-mediated lamellae formation in FLNa-null but not FLNa-expressing cells. Suppression of force-induced lamella formation was mediated by repeat 23 of FLNa, which also binds FilGAP, a recently discovered Rac GTPase-activating protein (GAP). We found that FilGAP is targeted to sites of force transfer by FLNa. This force-induced redistribution of FilGAP was essential for the suppression of Rac activity and lamellae formation in cells treated with tensile forces. Depletion of FilGAP by small interfering RNA, inhibition of FilGAP activity by dominant-negative mutation or deletion of its FLNa-binding domain, all resulted in a dramatic force-induced increase of the percentage of annexin-V–positive cells. FilGAP therefore plays a role in protecting cells against force-induced apoptosis, and this function is mediated by FLNa.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-08-0872) on January 14, 2009.

Address correspondence to: Yulia Shifrin (yulia.shifrin{at}utoronto.ca)

Abbreviations used: FLNa, filamin A; FilGAP, filamin A-associated RhoGAP; siRNA, small interfering RNA.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
N. J. Sniadecki
A Tiny Touch: Activation of Cell Signaling Pathways with Magnetic Nanoparticles
Endocrinology, February 1, 2010; 151(2): 451 - 457.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2009 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.