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The role of the Arp2/3 complex in the cytoskeleton organization and actin‐mediated sodium reabsorption in kidney epithelial cells

Actin cytoskeleton is an important mediator of a variety of functions in cells, including regulation of the epithelial Na+ channel (ENaC). One of the factors that control nucleation of actin filaments is the actin related protein 2/3 (Arp2/3) complex that potentiates actin polymerization. We have shown that treatment of principal cell line M‐1 with Arp2/3 complex inhibitors CK‐0944666 (CK‐666) and CK‐869 results in reorganization of F‐actin and decreases cell motility and lamellipodia formation. Compound concentrations used in this study neither caused loss of cell viability nor influenced the shape of the cells or the integrity of the monolayers. Furthermore, the action of the described compounds was not due to structural side effects since inactive analog of CK‐0944666, CK‐689, lacked the effect on cell motility. Inhibition of the Arp2/3 complex by CK‐666 precluded the effect of cortactin on ENaC; furthermore, it has been revealed that treatment with CK‐666 does not result in the loss of association between ENaC and cortactin. This finding was proved by patch‐clamp studies that showed that only a cortactin mutant unable to bind Arp2/3 had no influence on ENaC activity. Thus, Arp2/3 complex plays an important role in cell motility and F‐actin organization in the kidney cells. Moreover, Arp2/3 complex mediates renal Na+ transport via cortactin‐mediated regulation of ENaC. Supported by NIH (HL108880) and OPTEC.