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Journal of Cellular Biochemistry

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

Authors

  • Grace Choong,

    1. Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
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  • Ying Liu,

    1. Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
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  • Douglas M. Templeton

    Corresponding author
    1. Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8
    • Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building Rm. 6302, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
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  • Grace Choong and Ying Liu contributed equally to this work.

Abstract

The toxic metal ion cadmium (Cd2+) 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 Ca2+/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, Cd2+ 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 Cd2+. 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 Cd2+-dependent manner. These results add further insight into the mechanism of the CaMK-II-dependent effects of Cd2+ on cellular function. J. Cell. Biochem. 114: 1832–1842, 2013. © 2013 Wiley Periodicals, Inc.

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