Laboratory of Systems Neurobiology and Medicine

Research Projects

Mechanobiology of axon guidance and cell migration

Animals move and change their shape, using force generated by muscles. How cells do so? Actin polymerizes near the leading edges of neurite tips and migrating cells. We reported that shootin1a interacts with both the polymerizing actin filaments and the cell adhesion molecule L1-CAM at neurite tips, thereby generating traction force for neurite outgrowth. We are currently analyzing molecular mechanisms for generation and regulation of mechanical forces for axon guidance and neuronal migration. We also reported a new type of axon guidance mechanism (Grip & Slip mechanism) induced by the extracellular matrix protein Laminin.

Fig.7

Traction force microscopy to measure forces for axon guidance and neuronal migration

Reference

  1. Minegishi T, Fujikawa R, Kastian RF, Sakumura Y, Inagaki N, (2021)
    Analyses of actin dynamics, clutch coupling and traction force for growth cone advance, J. Vis. Exp. e63227. (LINK)
  2. Kastian RF, Minegishi T, Inagaki N, (2021)
    Simultaneous analyses of clutch coupling and actin polymerization in dendritic spines during chemical LTP, Star Protoc. 2, 100904.(LINK)
  3. Urasaki, A., Morishita, S., Naka, K., Uozumi, M., Abe, K., Huang, L., Watase, E., Nakagawa, O., Kawakami, K., Matsui, Y., Bessho, Y., and Inagaki, N.(2019)
    Shootins mediate collective cell migration and organogenesis of the zebrafish posterior lateral line system, Sci. Rep. 9:12156 . (LINK)
  4. Minegishi T., Uesugi Y., Kaneko N., Yoshida W., Sawamoto K.and Inagaki, N. (2018)
    Shootin1b mediates a mechanical clutch to produce force for neuronal migration, Cell Reports 25, 624-639(LINK)
    (EurekAlert!),(ScienceDaily),(Medicalxpress)
  5. Baba, K., Yoshida, W., Toriyama, M., Shimada, T., Manning, C.F., Saito, M., Kohno, K., Trimmer, J.S., Watanabe, R., and Inagaki, N. (2018)
    Gradient-reading and mechano-effector machinery for netrin-1?induced axon guidance. eLife 2018;7:e34593.(LINK)
    ( EurekAlert!),(ScienceDaily),(MedicalXpress),(Neuroscience News),(Faculty of 1000 prime special significance)
  6. Abe, K., Katsuno, H., Toriyama, M., Baba, K., Mori T., Hakoshima T, Kanemura Y., Watanabe, R. and Inagaki, N. (2018)
    Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis, Proc. Natl. Acad. Sci. USA,115, 2764-2769. doi:10.1073/pnas.1711667115 (LINK)
    (Medicalxpress),(ScienceDaily),(EurekAlert!),(AsianScientist)
  7. Kubo, Y., Baba, K., Toriyama, M., Minegishi, T., Sugiura, T., Kozawa, S., Ikeda, K., and Inagaki, N. (2015)
    Shootin1-cortactin interaction mediates signal-force transduction for axon outgrowth. J Cell Biol. 210, 663-676. (LINK)
  8. Toriyama, M., Kozawa, S., Sakumura, Y. and Inagaki, N. (2013)
    Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation, Current Biology 23, 529-534 (2013).(LINK)(Faculty of 1000 special significance)
  9. Shimada, T., Toriyama, M., Uemura, K., Kamiguchi, H., Sugiura, T., Watanabe, N. and Inagaki, N. (2008)
    Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth., J. Cell Biol. 181, 817-829.(LINK)

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