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

J. Biol. Chem., Vol. 281, Issue 16, 11260-11270, April 21, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/16/11260    most recent M512885200v2 M512885200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, L.-T. Articles by Runnels, L. W. Search for Related Content PubMed PubMed Citation Articles by Su, L.-T. Articles by Runnels, L. W. Social Bookmarking                      What's this?

TRPM7 Regulates Cell Adhesion by Controlling the Calcium-dependent Protease Calpain^*

Li-Ting Su, Maria A. Agapito, Mingjiang Li, William T. N. Simonson^¶, Anna Huttenlocher^¶, Raymond Habas^||, Lixia Yue, and Loren W. Runnels¹

From the Department of Pharmacology, University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, the Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, the ^¶Departments of Pediatrics and Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, and the ^||Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

m-Calpain is a protease implicated in the control of cell adhesion through focal adhesion disassembly. The mechanism by which the enzyme is spatially and temporally controlled is not well understood, particularly because the dependence of calpain on calcium exceeds the submicromolar concentrations normally observed in cells. Here we show that the channel kinase TRPM7 localizes to peripheral adhesion complexes with m-calpain, where it regulates cell adhesion by controlling the activity of the protease. Our research revealed that overexpression of TRPM7 in cells caused cell rounding with a concomitant loss of cell adhesion that is dependent upon the channel of the protein but not its kinase activities. Knockdown of m-calpain blocked TRPM7-induced cell rounding and cell detachment. Silencing of TRPM7 by RNA interference, however, strengthened cell adhesion and increased the number of peripheral adhesion complexes in the cells. Together, our results suggest that the ion channel TRPM7 regulates cell adhesion through m-calpain by mediating the local influx of calcium into peripheral adhesion complexes.

Received for publication, December 2, 2005 , and in revised form, January 23, 2006.

^* This work was supported by American Heart Association Grant 0335375T. 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 Figs. S1-S3.

¹ To whom correspondence should be addressed: Dept. of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Ln., Piscataway, NJ 08854. Tel.: 732-235-4593; Fax: 732-235-4073; E-mail: runnellw{at}umdnj.edu.

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

This article has been cited by other articles:

				M. Honda, F. Masui, N. Kanzawa, T. Tsuchiya, and T. Toyo-oka Specific knockdown of m-calpain blocks myogenesis with cDNA deduced from the corresponding RNAi Am J Physiol Cell Physiol, April 1, 2008; 294(4): C957 - C965. [Abstract] [Full Text] [PDF]

				B. Sontia, A. C.I. Montezano, T. Paravicini, F. Tabet, and R. M. Touyz Downregulation of Renal TRPM7 and Increased Inflammation and Fibrosis in Aldosterone-Infused Mice: Effects of Magnesium Hypertension, April 1, 2008; 51(4): 915 - 921. [Abstract] [Full Text] [PDF]

				R. M. Touyz Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1103 - H1118. [Abstract] [Full Text] [PDF]

				R. C. E. Wykes, M. Lee, S. M. Duffy, W. Yang, E. P. Seward, and P. Bradding Functional Transient Receptor Potential Melastatin 7 Channels Are Critical for Human Mast Cell Survival J. Immunol., September 15, 2007; 179(6): 4045 - 4052. [Abstract] [Full Text] [PDF]

				M. Li, J. Du, J. Jiang, W. Ratzan, L.-T. Su, L. W. Runnels, and L. Yue Molecular Determinants of Mg2+ and Ca2+ Permeability and pH Sensitivity in TRPM6 and TRPM7 J. Biol. Chem., August 31, 2007; 282(35): 25817 - 25830. [Abstract] [Full Text] [PDF]

				B. F. Bessac and A. Fleig TRPM7 channel is sensitive to osmotic gradients in human kidney cells J. Physiol., August 1, 2007; 582(3): 1073 - 1086. [Abstract] [Full Text] [PDF]

				V. Chubanov, K. P. Schlingmann, J. Waring, J. Heinzinger, S. Kaske, S. Waldegger, M. M. y Schnitzler, and T. Gudermann Hypomagnesemia with Secondary Hypocalcemia due to a Missense Mutation in the Putative Pore-forming Region of TRPM6 J. Biol. Chem., March 9, 2007; 282(10): 7656 - 7667. [Abstract] [Full Text] [PDF]

				M. Langeslag, K. Clark, W. H. Moolenaar, F. N. van Leeuwen, and K. Jalink Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists J. Biol. Chem., January 5, 2007; 282(1): 232 - 239. [Abstract] [Full Text] [PDF]

				B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]