title: TRPM7 regulates polarized cell movements.
abstract: 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.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Su
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hsiang-Chin
authors.initials: HC
authors.lastname: Chen
authors.forename: Omayra
authors.initials: O
authors.lastname: González-Pagán
authors.forename: Raymond
authors.initials: R
authors.lastname: Habas
authors.forename: Loren W
authors.initials: LW
authors.lastname: Runnels
mesh_terms: D016475:3T3 Cells; D000205:Actomyosin / Q000502:physiology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D027682:Cation Transport Proteins / Q000096:biosynthesis; D002413:Cations, Divalent; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D008274:Magnesium / Q000502:physiology; D051379:Mice; D034622:RNA Interference; D050053:TRPM Cation Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent; C501065:Slc41a2 protein, mouse; D050053:TRPM Cation Channels; D000205:Actomyosin; C421903:Trpm7 protein, mouse; D008274:Magnesium