HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 22, 16585-16598, June 1, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/22/16585    most recent M701011200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Papp, S. Articles by Opas, M. Search for Related Content PubMed PubMed Citation Articles by Papp, S. Articles by Opas, M. Social Bookmarking                      What's this?

Calreticulin Affects Fibronectin-based Cell-Substratum Adhesion via the Regulation of c-Src Activity^*

Sylvia Papp¹, Marc P. Fadel, Hugh Kim, Christopher A. McCulloch, and Michal Opas²

From the Department of Laboratory Medicine and Pathobiology and Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Calreticulin is an endoplasmic reticulum Ca²⁺-storage protein, which influences gene expression and cell adhesion. In this study, we show that calreticulin induces fibronectin gene expression and matrix deposition, leading to differences in cell spreading and focal adhesion formation in cells differentially expressing calreticulin. We further show that these effects of calreticulin occur via a c-Src-regulated pathway and that c-Src activity is inversely related to calreticulin abundance. Since c-Src is an important regulator of focal contact turnover, we investigated the effect of c-Src inhibition on cells differentially expressing calreticulin. Inhibition of c-Src rescued the poorly adhesive phenotype of the calreticulin-underexpressing cells in that they became well spread, commenced formation of numerous focal contacts, and deposited a rich fibronectin matrix. Importantly, we show that c-Src activity is dependent on releasable Ca²⁺ from the endoplasmic reticulum, thus implicating Ca²⁺-sensitive pathways that are affected by calreticulin in cell-substratum adhesion. We propose that calreticulin affects fibronectin synthesis and matrix assembly via the regulation of fibronectin gene expression. In parallel, calcium-dependent effects of calreticulin on c-Src activity influence the formation and/or stability of focal contacts, which are instrumental in matrix assembly and remodeling.

Received for publication, February 2, 2007

^* This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation of Ontario (to M. O.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1.

¹ Recipient of a Canada Graduate Scholarship from the CIHR.

² Member of the Heart and Stroke/Richard Lewar Centre of Excellence. To whom correspondence should be addressed: Dept. of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Medical Sciences Bldg., Rm.6326 Toronto, Ontario M5S 1A8, Canada. Tel.: 416-978-8947; Fax: 416-978-5959; E-mail: m.opas{at}utoronto.ca.

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

This article has been cited by other articles:

				E. Szabo, Y. Qiu, S. Baksh, M. Michalak, and M. Opas Calreticulin inhibits commitment to adipocyte differentiation J. Cell Biol., October 23, 2008; 182(1): 103 - 116. [Abstract] [Full Text] [PDF]

				L. B. Nanney, C. D. Woodrell, M. R. Greives, N. L. Cardwell, A. C. Pollins, T. A. Bancroft, A. Chesser, M. Michalak, M. Rahman, J. W. Siebert, et al. Calreticulin Enhances Porcine Wound Repair by Diverse Biological Effects Am. J. Pathol., September 1, 2008; 173(3): 610 - 630. [Abstract] [Full Text] [PDF]