title: Cadmium affects focal adhesion kinase (FAK) in mesangial cells: involvement of CaMK-II and the actin cytoskeleton.
abstract: The toxic metal ion cadmium (Cd(2+)) induces pleiotropic effects on cell death and survival, in part through effects on cell signaling mechanisms and cytoskeletal dynamics. Linking these phenomena appears to be calmodulin-dependent activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II). Here we show that interference with the dynamics of the filamentous actin cytoskeleton, either by stabilization or destabilization, results in disruption of focal adhesions at the ends of organized actin structures, and in particular the loss of vinculin and focal adhesion kinase (FAK) from the contacts is a result. Low-level exposure of renal mesangial cells to CdCl2 disrupts the actin cytoskeleton and recapitulates the effects of manipulation of cytoskeletal dynamics with biological agents. Specifically, Cd(2+) treatment causes loss of vinculin and FAK from focal contacts, concomitant with cytoskeletal disruption, and preservation of cytoskeletal integrity with either a calmodulin antagonist or a CaMK-II inhibitor abrogates these effects of Cd(2+). Notably, inhibition of CaMK-II decreases the migration of FAK-phosphoTyr925 to a membrane-associated compartment where it is otherwise sequestered from focal adhesions in a Cd(2+)-dependent manner. These results add further insight into the mechanism of the CaMK-II-dependent effects of Cd(2+) on cellular function.
authors: Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
authors: Grace
authors: G
authors: Choong
authors: Ying
authors: Y
authors: Liu
authors: Douglas M
authors: DM
authors: Templeton
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002460:Cell Line; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats
chemical_list: D002104:Cadmium; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium