Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2847K) PDF+supp data (4083K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frantz, C. Articles by Barber, D. L. Search for Related Content PubMed PubMed Citation Articles by Frantz, C. Articles by Barber, D. L. Related Collections Related In this Issue article Social Bookmarking                            What's this?

Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

¹ Department of Cell and Tissue Biology, University of California, San Francisco, CA 94143
² Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158
³ Department of Anatomy and Structural Biology and ⁴ Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, New York, NY 10461

Correspondence to Diane L. Barber: diane.barber{at}ucsf.edu

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H⁺ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics.

© 2008 Frantz et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related In this Issue article

Cofilin activity is a total coincidence

Caitlin Sedwick
J. Cell Biol. 2008 183: 753. [Full Text] [PDF]

This article has been cited by other articles:

• Leyman, S., Sidani, M., Ritsma, L., Waterschoot, D., Eddy, R., Dewitte, D., Debeir, O., Decaestecker, C., Vandekerckhove, J., van Rheenen, J., Ampe, C., Condeelis, J., Van Troys, M. (2009). Unbalancing the Phosphatidylinositol-4,5-bisphosphate-Cofilin Interaction Impairs Cell Steering. Mol. Biol. Cell 20: 4509-4523 [Abstract] [Full Text]  
• Meima, M. E., Webb, B. A., Witkowska, H. E., Barber, D. L. (2009). The Sodium-Hydrogen Exchanger NHE1 Is an Akt Substrate Necessary for Actin Filament Reorganization by Growth Factors. J. Biol. Chem. 284: 26666-26675 [Abstract] [Full Text]  
• Marshall, T. W., Aloor, H. L., Bear, J. E. (2009). Coronin 2A regulates a subset of focal-adhesion-turnover events through the cofilin pathway. J. Cell Sci. 122: 3061-3069 [Abstract] [Full Text]  
• Monshausen, G. B., Bibikova, T. N., Weisenseel, M. H., Gilroy, S. (2009). Ca2+ Regulates Reactive Oxygen Species Production and pH during Mechanosensing in Arabidopsis Roots. Plant Cell 21: 2341-2356 [Abstract] [Full Text]  
• Sin, W.-C., Moniz, D. M., Ozog, M. A., Tyler, J. E., Numata, M., Church, J. (2009). Regulation of Early Neurite Morphogenesis by the Na+/H+ Exchanger NHE1. J. Neurosci. 29: 8946-8959 [Abstract] [Full Text]  
• van Rheenen, J., Condeelis, J., Glogauer, M. (2009). A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J. Cell Sci. 122: 305-311 [Abstract] [Full Text]  
• Sedwick, C. (2008). Cofilin activity is a total coincidence. JCB 183: 753-753 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents