KIF17 regulates RhoA-dependent actin remodeling at epithelial cell-cell adhesions

Abstract

The kinesin KIF17 localizes at MT plus-ends and contributes to regulation of MT stabilization, and epithelial polarization. We now show that KIF17 localizes at cell-cell adhesions and that KIF17 depletion inhibits accumulation of actin at the apical pole of cells grown in 3D organotypic cultures and alters the distribution of actin and E-cadherin in cells cultured in 2D on solid supports. Overexpression of full-length KIF17 constructs or truncation mutants containing the N-terminal motor domain resulted in accumulation of newly incorporated GFP-actin into junctional actin foci, cleared E-cadherin from cytoplasmic vesicles and stabilized cell-cell adhesions to challenge with calcium depletion. Expression of these KIF17 constructs also increased cellular levels of active RhoA, while active RhoA was diminished in KIF17-depleted cells. Inhibition of Rho or its effector ROCK, or expression of LIMK1 kinase-dead or activated cofilinS3A inhibited KIF17-induced junctional actin accumulation. Interestingly, KIF17 activity toward actin depends on the motor domain but is independent of MT binding. Together, these data show that KIF17 can modify Rho-GTPase signaling to influence junctional actin and the stability of the apical junctional complex of epithelial cells.