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

J Cell Sci. 2007 Aug 15;120(Pt 16):2828-37. doi: 10.1242/jcs.03477. Epub 2007 Jul 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Adhesion
  • Cell Movement
  • Cell-Matrix Junctions / metabolism*
  • Crk-Associated Substrate Protein / metabolism
  • Cytoskeleton / metabolism
  • Focal Adhesions / metabolism
  • HeLa Cells
  • Humans
  • LIM Domain Proteins
  • Phosphotyrosine / metabolism
  • Proteasome Endopeptidase Complex
  • Protein Transport
  • Proto-Oncogene Proteins c-crk / metabolism
  • Pseudopodia / metabolism
  • Stress Fibers / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / metabolism*
  • Xenopus
  • rac1 GTP-Binding Protein / metabolism
  • rho GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Crk-Associated Substrate Protein
  • LIM Domain Proteins
  • PSMC5 protein, human
  • Proto-Oncogene Proteins c-crk
  • Transcription Factors
  • Phosphotyrosine
  • Proteasome Endopeptidase Complex
  • ATPases Associated with Diverse Cellular Activities
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein