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Regulatory mechanisms of the WAVE regulatory complex

Dynamics of the actin cytoskeleton are essential to all eukaryotic cells. The WAVE regulatory complex (WRC) is a key player in controlling actin dynamics during many cellular processes including morphogenesis, adhesion, migration and cytokinesis. The WRC activates the Arp2/3 complex to stimulate actin polymerization adjacent to membranes.

Being a large, cytoplasmic and auto-inhibited protein complex, the WRC serves as a signaling platform that integrates a large variety of cellular cues to stimulate actin polymerization at specific membrane sites. In this process, the WRC is recruited to membranes by different membrane-anchored ligands (acidic lipids, receptors, etc) and biochemically activated by ligands such as the small GTPase, Rac. Previous biochemical and structural work has shed light on how the WRC is inhibited.

However, the mechanisms that underlie its activation and link its activity to specific membrane locations remain poorly understood. I hope to solve these puzzles in order to fully understand the regulation of the WRC.

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