Rac1 and EMT: a dangerous liaison?

Rac1 was originally identified in 1989 in human platelets as a substrate of the botulinum toxin from which its name derives: Ras-related C3 botulinum toxin substrate (1). Rac1 belongs to the Rho family of small guanosine triphosphatases (GTPases), and is ubiquitously expressed. It exists in two conformational states, an inactive GDP-bound form and an active GTP-bound form. The transition from one form to another occurs upon stimuli and depends on GTPase-activating proteins (GAPs), which inactivate Rac1, and guanine nucleotide exchange factors (GEFs), which convert Rac1 to its active form. Among GEFs, the trimeric complex SOS1/EPS8/ABI1 plays a role in Rac regulation. Dissection of the complex shows that SOS1 is central because it supports the catalytic component of the complex, and both ABI1, also named EPS8 SH3 domain binding protein, and EPS8 with its SOS1 binding domain, allow the cohesion of this complex. Functionally, Rac1 was the subject of numerous studies highlighting diverse and broad cellular functions since its discovery. Rac1 serves as a conformational switch in several signal transduction pathways at the origin of its biological functions. One of its primary function identified, far away the most characterized, is the regulation of actin cytoskeleton organization and dynamics, in the migratory structures such as filopodia and lamellipodia. Subsequently, other Rac1 functions were evidenced including roles in cell polarity, gene expression, cell-cycle progression, and cell survival.