WASPs and WAVEs: From molecular function to physiology in hematopoietic cells

• WASP family proteins, including WASPs and WAVEs, are the best characterized nucleation promoting factors, i.e. the activators of the Arp2/3 complex, and new members are still being identified.
• WASP is a prototype of the WASP family. Very recently, the loss of WIP, a WASP chaperon, led to development of a WAS like genetic disorder.
• WAVEs1–3 markedly differ in their tissue distribution. In addition, WAVE2 may selectively prefer IRSp53 as a ligand, potentially its unique indispensable role in lamellipodia of mammalian cells.
• The essential roles of WASP/N-WASP in the development of podosomes, invadopodia, and the related structures have been well recognized.
• N-WASP reportedly is critical in vesicular trafficking. So is a new WASP family member WASH.

The actin cytoskeleton is critically involved in a variety of cell functions. The Arp2/3 complex mediates branching of filamentous actin. The members of the Wiskott–Aldrich syndrome protein (WASP) family are major regulators of the complex. As such, the family proteins are also involved in numerous aspects of cell biology. In this short review, we first define the expanding WASP family. Next, we compare the domain structure of the members, and explain the known or proposed functions of each domain or region. Finally, we demonstrate the well-characterized roles of the proteins in specific cellular functions.