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.
Highlights
The actin cytoskeleton provides mechanical support for the cell, determines cell shape, enables cell movement, and participates in cell-matrix and cell-cell adhesions
ZRP-1 is localized to focal adhesions and cell-cell adhesions We generated rabbit polyclonal antibodies against a peptide corresponding to amino acid residues 10 to 25 of human ZRP1
These results indicate that ZRP-1 is localized at cell-matrix and cell-cell adhesion sites
Summary
The actin cytoskeleton provides mechanical support for the cell, determines cell shape, enables cell movement, and participates in cell-matrix and cell-cell adhesions. It is well established that the actin cytoskeleton is regulated by Rho GTPases. The three prototypic Rho GTPases, RhoA, Rac and Cdc, are best known for their effects on the actin cytoskeleton. When a cell is migrating, it extends membrane protrusions or lamellipodia through a Rac-dependent mechanism. At the leading edge of an extended protrusion, focal complexes containing integrin receptors and cytoskeletal proteins are formed in a Rac-dependent manner (Nobes and Hall, 1999). A Rho-dependent mechanism promotes growth of the focal complex into the focal adhesion (Greenwood and MurphyUllrich, 1998; Nobes and Hall, 1999). Focal adhesion provides a tension point for contractile forces to move the cell forward (Horwitz et al, 1999)
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