Decoding Rho GTPase signalling networks in directed cell migration

Small G proteins are molecular switches in the realm of cell biology, switching from the GTP-bound active form to the GDP-bound inactive form. They participate in controlling various essential cellular functions, one of which is cell migration. Cell migration is a sine qua non for the proper functioning of the cell, as it aids in a litany of cellular processes, including embryonic development, morphogenesis, organogenesis, wound healing, and pathogenic states such as cancer metastasis. Amongst the five families of small G proteins (with over 150 members), Rho GTPase family is known to have significant roles in cell migration. Rho GTPases (primarily RhoA, Rac1, and Cdc42) translate extracellular cues into the spatiotemporal coordination of the actin cytoskeleton, allowing cells to polarize, migrate and navigate their environment. They integrate biochemical and biophysical signals through guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rac1 and Cdc42 are known to act at the front end of a migrating cell and aid in cell polarisation, formation of protrusions and adhesive structures, while RhoA, though having overlapping roles, majorly functions at the cell rear, where it regulates cell body contraction and tail detachment, all of which we look into elaborately in this review. We also discuss the roles played by the other Rho GTPases in cell migration and have touched on the physiological and pathological impacts that Rho GTPase-regulated cell migration has on human health.