View the Current Issue

Article

  • The EMBO Journal (2007) 26, 1487 - 1498
  • doi:10.1038/sj.emboj.7601599

Published online: 22 February 2007

Integrin-mediated adhesion orients the spindle parallel to the substratum in an EB1- and myosin X-dependent manner

Fumiko Toyoshima1,2 and Eisuke Nishida1

  1. Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan
  2. Precursory Research for Embryonic Science and Technology, JST, Honcho Kawaguchi, Saitama, Japan

Correspondence to:

Fumiko Toyoshima, Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. Tel.: +81 75 753 9428; Fax: +81 75 753 4235; E-mail: ftoyoshima@lif.kyoto-u.ac.jp

Received 9 June 2006; Accepted 22 January 2007

The orientation of mitotic spindles is tightly regulated in polarized cells, but it has been unclear whether there is a mechanism regulating spindle orientation in nonpolarized cells. Here we show that integrin-dependent cell adhesion to the substrate orients the mitotic spindle of nonpolarized cultured cells parallel to the substrate plane. The spindle is properly oriented in cells plated on fibronectin or collagen, but misoriented in cells on poly-L-lysine or treated with the RGD peptide or anti-beta1-integrin antibody, indicating requirement of integrin-mediated cell adhesion for this mechanism. Remarkably, this mechanism is independent of gravitation or cell–cell adhesion, but requires actin cytoskeleton and astral microtubules. Furthermore, myosin X and the microtubule plus-end-tracking protein EB1 are shown to play a role in this mechanism through remodeling of actin cytoskeleton and stabilization of astral microtubules, respectively. Our results thus uncover the existence of a mechanism that orients the spindle parallel to the cell–substrate adhesion plane, and identify crucial factors involved in this novel mechanism.

  • Keywords:

    • cell–substrate adhesion,
    • EB1,
    • integrin,
    • myosin X,
    • spindle orientation