Inside view of cell locomotion through single-molecule: fast F-/G-actin cycle and G-actin regulation of polymer restoration.
The actin cytoskeleton drives cell locomotion and tissue remodeling. The invention of live-cell fluorescence single-molecule imaging opened a window for direct viewing of the actin remodeling processes in the cell. Since then, a number of unanticipated molecular functions have been revealed. One is the mechanism of F-actin network breakdown. In lamellipodia, one third of newly polymerized F-actin disassembles within 10 seconds. This fast F-actin turnover is facilitated by the filament severing/disrupting activity involving cofilin and AIP1. Astoundingly fast dissociation kinetics of the barbed end interactors including capping protein suggests that F-actin turnover might proceed through repetitive disruption/reassembly of the filament near the barbed end. The picture of actin polymerization is also being revealed. At the leading edge of the cell, Arp2/3 complex is highly activated in a narrow edge region. In contrast, mDia1 and its related Formin homology proteins display a long-distance directional molecular movement using their processive actin capping ability. Recently, these two independently-developed projects converged into a discovery of the spatiotemporal coupling between mDia1-mediated filament nucleation and actin disassembly. Presumably, the local concentration fluctuation of G-actin regulates the actin nucleation efficiency of specific actin nucleators including mDia1. Pharmacological perturbation and quantitative molecular behavior analysis synergize to reveal hidden molecular linkages in the actin turnover cycle and cell signaling.
Watanabe
Naoki
N
Department of Pharmacology, Kyoto University Faculty of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan. naoki-w@mfour.med.kyoto-u.ac.jp
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D006801:Humans; D007700:Kinetics; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D011554:Pseudopodia / Q000378:metabolism
D000199:Actins