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First published online 24 July 2007
doi: 10.1242/jcs.03477


Journal of Cell Science 120, 2828-2837 (2007)
Published by The Company of Biologists 2007
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Research Article

ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions

Chen-Yu Bai1,*, Miho Ohsugi1,*, Yoshinori Abe2 and Tadashi Yamamoto1,{ddagger}

1 Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
2 Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan

{ddagger} Author for correspondence (e-mail: tyamamot{at}ims.u-tokyo.ac.jp)

Accepted 29 May 2007

Focal adhesion protein ZRP-1/TRIP6 has been implicated in actin reorganization and cell motility. The role of ZRP-1, however, remained obscure because previously reported data are often conflicting one another. In the present study, we examined roles of ZRP-1 in HeLa cells. ZRP-1 is localized to the cell-cell contact sites as well as to cell-matrix contact sites in HeLa cells. RNA-interference-mediated depletion of ZRP-1 from HeLa cells revealed that ZRP-1 is essential not only for the formation of stress fibers and assembly of mature focal adhesions, but also for the actin reorganization at cell-cell contact sites and for correct cell-cell adhesion and, thus, for collective cell migration. Impairment of focal adhesions and stress fibers caused by ZRP-1 depletion has been associated with reduced tyrosine phosphorylation of FAK. However, maturation of focal adhesions could not be recovered by expression of active FAK. Interestingly, stress fibers in ZRP-1-depleted cells were ameliorated by exogenous expression of RhoA. We also found that total Rac1 activity is elevated in ZRP-1-depleted cells, resulting in abnormal burst of actin polymerization and dynamic membrane protrusions. Taken together, we conclude that that ZRP-1 plays a crucial role in coupling the cell-matrix/cell-cell-contact signals with Rho GTPase-mediated actin remodeling by localizing at cell-matrix and cell-cell contact sites.

Key words: Actin reorganization, Focal adhesion, Cell-cell adhesion, Collective cell migration, Rho family GTPase







© The Company of Biologists Ltd 2007