TRPM7 (transient receptor potential melastatin 7) is a Ca2+- and Mg2+-permeant ion channel in possession of its own kinase domain. As a kinase, the protein has been linked to the control of actomyosin contractility, whereas the channel has been found to regulate cell adhesion as well as cellular Mg2+ homoeostasis. In the present study we show that depletion of TRPM7 by RNA interference in fibroblasts alters cell morphology, the cytoskeleton, and the ability of cells to form lamellipodia and to execute polarized cell movements. A pulldown-purification assay revealed that knockdown of TRPM7 prevents cells from activating Rac and Cdc42 (cell division cycle 42) when stimulated to migrate into a cellular wound. Re-expression of TRPM7 reverses these phenotypic changes, as does, unexpectedly, expression of a kinase-inactive mutant of TRPM7. Surprisingly, expression of the Mg2+ transporter SLC41A2 (solute carrier family 41 member 2) is also effective in restoring the change in cell morphology, disruption of the cytoskeleton and directional cell motility caused by depletion of the channel-kinase. The results of the present study uncover an essential role for Mg2+ in the control of TRPM7 over the cytoskeleton and its ability to regulate polarized cell movements.
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Research Article|
February 24 2011
TRPM7 regulates polarized cell movements Available to Purchase
Li-Ting Su;
*Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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Wei Liu;
Wei Liu
1
†Department of Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, U.S.A.
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Hsiang-Chin Chen;
Hsiang-Chin Chen
*Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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Omayra González-Pagán;
Omayra González-Pagán
*Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, U.S.A.
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Raymond Habas;
Raymond Habas
3
†Department of Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, U.S.A.
3Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Loren W. Runnels
Loren W. Runnels
3
*Department of Pharmacology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, U.S.A.
3Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Publisher: Portland Press Ltd
Received:
October 12 2010
Revision Received:
November 29 2010
Accepted:
January 06 2011
Accepted Manuscript online:
January 06 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 434 (3): 513–521.
Article history
Received:
October 12 2010
Revision Received:
November 29 2010
Accepted:
January 06 2011
Accepted Manuscript online:
January 06 2011
Citation
Li-Ting Su, Wei Liu, Hsiang-Chin Chen, Omayra González-Pagán, Raymond Habas, Loren W. Runnels; TRPM7 regulates polarized cell movements. Biochem J 15 March 2011; 434 (3): 513–521. doi: https://doi.org/10.1042/BJ20101678
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