Regulation of the Scar/WAVE complex in migrating cells: A summary of our understanding

Eukaryotic cell migration requires continuous supply of actin polymers at the leading edges to make and extend lamellipodia or pseudopodia. Linear and branched filamentous actin polymers fuel cell migration. Branching of actin polymers in the lamellipodia/pseudopodia is facilitated by the actin-related protein (Arp) 2/3 complex, whose function is essentially controlled by the Scar/WAVE complex. In cells, the Scar/WAVE complex remains inactive, and its activation is a highly regulated and complex process. In response to signalling cues, GTP-bound Rac1 associates with Scar/WAVE and causes activation of the complex. Rac1 is essential but not sufficient for the activation of the Scar/ WAVE complex, and it requires multiple regulators, such as protein interactors and modifications (phosphorylation, ubiquitylation, etc.). Although our understanding of the regulation of the Scar/WAVE complex has improved over the last decade, it remains enigmatic. In this review, we have provided an overview of actin polymerization and discussed the importance of various regulators of Scar/WAVE activation.