title: ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions.
abstract: 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.
authors.affiliation: Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Bai
authors.forename: Miho
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Abe
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins; D019000:Phosphotyrosine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D021381:Protein Transport; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D014981:Xenopus; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D050719:Crk-Associated Substrate Protein; D060588:LIM Domain Proteins; C092282:PSMC5 protein, human; D050737:Proto-Oncogene Proteins c-crk; D014157:Transcription Factors; D019000:Phosphotyrosine; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein