Department of Biomolecular Sciences
Division of Molecular Biosystems

Molecular Cell Biology 分野

p_mizuno
Kensaku Mizuno
キャンパス Aobayama キャンパス
専攻分野 Laboratory of Molecular Cell Biology
連絡先 Tel:+81-22-795-6676 Fax:+81-22-795-6678
E-mail kmizunoatbiology.tohoku.ac.jp
ホームページ http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/
経歴
1975 B.S., Faculty of Science, Osaka University
1977 M.S., Graduate School of Science, Osaka University
1979 Assistant Professor, Department of Biochemistry, Miyazaki Medical College
1983 Ph.D., Osaka University
1989 -
1990
Foreign Researcher, Department of Pharmacology, University of California, San Diego
1990 Associate Professor, Faculty of Science, Kyushu University
1999 Professor, Graduate School of Science, Tohoku University
2001 Professor, Graduate School of Life Sciences, Tohoku University
著書・論文

Yang, N., Higuchi, O., Ohashi, K., Nagata, K., Wada, A., Kangawa, K., Nishida, E., and Mizuno, K. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature, 393, 809-812 (1998)

Nagata-Ohashi, K., Ohta, Y., Goto, K., Chiba, S., Mori, R., Nishita, M., Ohashi, K., Kousaka, K., Iwamatsu, A., Niwa, R., Uemura, T., and Mizuno, K. A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia. J. Cell Biol., 165, 465-471 (2004).

Nishita, M., Tomizawa, C., Yamamoto, M., Horita, Y., Ohashi, K., and Mizuno K. Spatial and temporal regulation of cofilin activity by LIM-kinase and Slingshot is critical for directional cell migration. J. Cell Biol., 171, 349-359 (2005).

Kiuchi, T., Ohashi, K., Kurita, S., and Mizuno, K. Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers. J. Cell Biol., 177, 465-476 (2007).

Chiba, S., Ikeda, M., Katsunuma, K., Ohashi, K., and Mizuno, K. MST2- and Furry-mediated activation of NDR1 is critical for precise alignment of mitotic chromosomes. Curr. Biol., 19, 675-681 (2009).

Kiuchi, T., Nagai, T., Ohashi, K., and Mizuno, K. Measurements of spatiotemporal changes in G-actin concentration reveal its effect on stimulus-induced actin assembly and lamellipodium extension. J. Cell Biol., 193, 365-380 (2011).

Chiba, S., Amagai, Y., Homma, Y., Fukuda, M., and Mizuno, K. NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15. EMBO J., 32, 874-885 (2013).

Ohashi, K., Sampei, K., Nakagawa, M., Uchiumi, N., Amanuma, T., Aiba, S., Oikawa, M., and Mizuno, K. Damnacanthal, an effective inhibitor of LIM-kinase, inhibits cell migration and invasion. Mol. Biol. Cell, 25, 828-840 (2014).

所属学会 Japanese Biochemical Society, Molecular Biology Society of Japan, Japan Society for Cell Biology, American Society for Cell Biology
担当講義 Life Science A, Molecular Cell Biology (undergraduate), Cellular signaling (graduate)

最近の研究について

Our research group investigates the molecular mechanisms underlying cell migration, morphogenesis, and division. We focus on two processes that are fundamental to various cell responses and activities:

The roles of cytoskeletal remodeling in mechanosensing and tubule formation
Actin filament dynamics and reorganization play essential roles in various cellular events, including cell migration, morphogenesis, division, polarity formation, and vesicle transport. Actin dynamics are spatially and temporally regulated by a large number of actin-binding proteins. Cofilin is an actin-binding protein that promotes actin assembly/disassembly dynamics through its severing activity on actin filaments. We previously showed that cofilin is inactivated by phosphorylation of Ser-3 by LIM-kinase (LIMK) and testicular protein kinase (TESK), and is reactivated by dephosphorylation by the Slingshot (SSH) family of protein phosphatases. We also showed that these kinases and phosphatases play crucial roles in cell motility, chemotaxis, division, neurite outgrowth, and cancer cell invasion, through regulating cofilin activity and actin dynamics. We are now focusing on the roles of actin cytoskeletal dynamics in mechanical stress responses and tubule formation, using live-cell imaging and biochemical approaches in 2D- or 3D-cultured mammalian cells.

The molecular mechanisms of cilium formation and ciliophathy
Primary cilia (non-motile cilia) are antenna-like sensory organelles protruding from the plasma membrane of many growth-arrested cells. Primary cilia extend a microtubule-based axoneme from the mother centriole-derived basal body. Various signaling receptors and ion channels are enriched on ciliary membranes, allowing primary cilia to sense and transmit many chemical and mechanical cues from outside of the cell. Since primary cilia are required for the development and homeostasis of many tissues, defects in primary cilium formation or function cause diverse genetic disorders, collectively called ciliopathies, with a complex set of symptoms, including polycystic kidney disease, retinal degeneration, and neurological defects. Primary cilia are formed in response to growth inhibitory signals. We investigate the molecular mechanisms of ciliogenesis, with a particular emphasis on the cell cycle-dependent conversion of the mother centriole to the basal body in the early stage of ciliogenesis. Our research is focused on the roles of protein kinases that are involved in growth arrest signal-induced ciliogenesis.

メッセージ

I encourage anyone interested in our research to contact us without hesitation. We welcome motivated people.