Cadmium affects focal adhesion kinase (FAK) in mesangial cells: Involvement of CaMK‐II and the actin cytoskeleton

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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.

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