Cadmium favors F-actin depolymerization in rat renal mesangial cells by site-specific, disulfide-based dimerization of the CAP1 protein.

Cadmium favors F-actin depolymerization in rat renal mesangial cells by site-specific, disulfide-based dimerization of the CAP1 protein.
Arch Toxicol. 2017 Dec 08;:
Authors: Liu Y, Xiao W, Shinde M, Field J, Templeton DM
Abstract
Cadmium is a toxic metal that produces oxidative stress and has been shown to disrupt the actin cytoskeleton in rat renal mesangial cells (RMC). In a survey of proteins that might undergo Cd2+-dependent disulfide crosslinking, we identified the adenylyl cyclase-associated protein, CAP1, as undergoing a dimerization in response to Cd2+ (5-40 µM) that was sensitive to disulfide reducing agents, was reproduced by the disulfide crosslinking agent diamide, and was shown by site-directed mutagenesis to involve the Cys29 residue of the protein. Reactive oxygen species are not involved in the thiol oxidation, and glutathione modulates background levels of dimer. CAP1 is known to enhance cofilin's F-actin severing activity through binding to F-actin and cofilin. F-actin sedimentation and GST-cofilin pulldown studies of CAP1 demonstrated enrichment of the CAP1 dimer's association with cofilin, and in the cofilin-F-actin pellet, suggesting that Cd2+-induced dimer increases the formation of a CAP1-cofilin-F-actin complex. Both siRNA-based silencing of CAP1 and overexpression of a CAP1 mutant lacking Cys29 (and therefore, incapable of dimerization in response to Cd2+) increased RMC viability and provided some protectio...

Source: Archives of Toxicology - December 8, 2017 Category: Toxicology Authors: Liu Y, Xiao W, Shinde M, Field J, Templeton DM Tags: Arch Toxicol Source Type: research