Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement

TLDR

Cell movement is essential for embryonic tissue patterning, adult repair, and immune cell trafficking, and in animal cells it is driven by coordinated actin filament assembly and disassembly during crawling. The study aimed to analyze how the small GTPases Rho, Rac, and Cdc42 regulate actin organization to influence primary embryo fibroblast migration. This analysis was performed using an in vitro wound‑healing assay with primary embryo fibroblasts. Rac is required for lamellipodial protrusion and forward movement; Cdc42 maintains cell polarity and directs Golgi orientation; Rho sustains adhesion without stress fibers or focal adhesions; Ras controls focal adhesion and stress‑fiber turnover, and together these four GTPases cooperate to promote cell movement.

Abstract

Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.