The motor activity of myosin-X promotes actin fiber convergence at the cell periphery to initiate filopodia formation

Filopodia are actin- rich fingerlike protrusions found at the leading edge of migrating cells and are believed to play a role in directional sensing. Previous studies have shown that myosin- X ( myoX) promotes filopodia formation and that this is mediated through its ability to deliver specific cargoes to the cell periphery ( Tokuo, H., and M. Ikebe. 2004. Biochem Biophys. Commun. 319: 214 220; Zhang, H., J. S. Berg, Z. Li, Y. Wang, P. Lang, A. D. Sousa, A. Bhaskar, R. E. Cheney, and S. Stromblad. 2004. Nat. Cell Biol. 6: 523 - 531; Bohil, A. B., B. W. Robertson, and R. E. Cheney. 2006. Proc. Natl. Acad. Sci. USA. 103: 12411 - 12416; Zhu, X. J., C. Z. Wang, P. G. Dai, Y. Xie, N. N. Song, Y. Liu, Q. S. Du, L. Mei, Y. Q. Ding, and W. C. Xiong. 2007. Nat. Cell Biol. 9: 184 - 192). In this study, we show that the motor function of myoX and not the cargo function is critical for initiating filopodia formation. Using a dimer- inducing technique, we find that myoX lacking its cargo- binding tail moves laterally at the leading edge of lamellipodia and induces filopodia in living cells. We conclude that the motor function of the two- headed form of myoX is critical for actin reorganization at the leading edge, leading to filopodia formation.