He, KangminSakai, TsuyoshiTsukasaki, YoshikazuWatanabe, Tomonobu M.Ikebe, Mitsuo2017-12-062017He, Kangmin, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Tomonobu M. Watanabe, and Mitsuo Ikebe. 2017. “Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.” Scientific Reports 7 (1): 13685. doi:10.1038/s41598-017-06147-6. http://dx.doi.org/10.1038/s41598-017-06147-6.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492218Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell’s leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell’s leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.en-USJournal Article2017-12-0610.1038/s41598-017-06147-6