Regulation of the Cytoskeleton by Kinesins

Kinesins are motor proteins that associate with microtubules. The position of the motor domain has been linked to kinesin function. While amino-terminal and carboxy-terminal localization of the motor domain is linked to cargo transport, kinesins with the motor domain in the middle (M-kinesins) have a role in microtubule depolymerization. The kinesin-13 family consists of four M-kinesins, KIF2A, KIF2B, KIF2C, and KIF24. These proteins regulate the cytoskeleton through their microtubule depolymerizing activity. All four kinesins have reported functions in mitosis, while little is known about their roles in interphase. KIF2A and KIF2C are upregulated in cancer cells and the increased protein expression influences cell migration and invasiveness. In order to understand how KIF2A and KIF2C influence migration, we analyzed the microtubule and actin cytoskeleton in cells manipulated for kinesin expression. We found that depletion of KIF2A increases the number of focal adhesions and stress fibers and results in defects in cell spreading. KIF2A does not influence the dynamics of focal adhesion assembly or disassembly. In contrast, depletion of KIF2C prevents re-formation of focal adhesions. has little or no effect on the actin cytoskeleton. Here we uncovered a functional divergence in regulation of the cytoskeleton between KIF2A and KIF2C. Furthermore, this is the first time that an M-kinesin, which does not transport cargo, has been shown to influence focal adhesion dynamics.