Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
It is reported here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell periphery, filopodia, in addition to stress fibers, and rho controls the assembly of focal adhesion complexes.
This review presents the best characterized of these biochemical pathways that control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division.
Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells and their ability to influence cell polarity, microtubule dynamics, membrane transport pathways and transcription factor activity is probably just as significant.
Rho, a ras-related GTP-binding protein, rapidly stimulated stress fiber and focal adhesion formation when microinjected into serum-starved Swiss 3T3 cells, implying that rho is essential specifically for the coordinated assembly of focal adhesions and stress fibers induced by growth factors.
The main focus of this review will be Rho, Rac and Cdc42, the three best characterized mammalian Rho GTPases, though the genetic analysis of RhoGTPases in lower eukaryotes is making increasingly important contributions to this field.
It is proposed that rac and rho are essential components of signal transduction pathways linking growth factors to the organization of polymerized actin and that growth factors act through rac to stimulate this rho-dependent response.
All the evidence points to GEFs being the critical mediators of Rho GTPase activation, and this paper reviews the present understanding of how they do this.
Two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.
It is concluded that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.