Regulation of actin assembly by SCAR/WAVE proteins

Abstract

Actin reorganization is a tightly regulated process that co-ordinates complex cellular events, such as cell migration, chemotaxis, phagocytosis and adhesion, but the molecular mechanisms that underlie these processes are not well understood. SCAR (suppressor of cAMP receptor)/WAVE [WASP (Wiskott-Aldrich syndrome protein)-family verprolin homology protein] proteins are members of the conserved WASP family of cytoskeletal regulators, which play a critical role in actin dynamics by triggering Arp2/3 (actin-related protein 2/3)-dependent actin nucleation. SCAR/WAVEs are thought to be regulated by a pentameric complex which also contains Abi (Abl-interactor), Nap (Nck-associated protein), PIR121 (p53-inducible mRNA 121) and HSPC300 (haematopoietic stem progenitor cell 300), but the structural organization of the complex and the contribution of its individual components to the regulation of SCAR/WAVE function remain unclear. Additional features of SCAR/WAVE regulation are highlighted by the discovery of other interactors and distinct complexes. It is likely that the combinatorial assembly of different components of SCAR/WAVE complexes will prove to be vital for their roles at the centre of dynamic actin reorganization.

Invasive Podosomes and Myoblast Fusion

“…For example, Rac is thought to activate and/or localize Scar (also known as WAVE), a nucleation promoting factor (NPF) for the Arp2/3 complex, which is a seven-protein complex with actin nucleation activity (for review see Kurisu & Takenawa, 2009; Stradal & Scita, 2006; Takenawa & Suetsugu, 2007). Scar resides in a heteropentameric Scar complex with Kette (Nap1/Hem), Sra1 (PIR121/CYFIP), Abi, and HSPC300 (for review see Ibarra, Pollitt, & Insall, 2005). Both the Scar and Arp2/3 complexes are essential for myoblast fusion (Berger et al, 2008; Richardson, Beckett, Nowak, & Baylies, 2007; Schroter et al, 2004).…”

The SCAR/WAVE complex is necessary for proper regulation of traction stresses during amoeboid motility

“…Unlike mammalian cells lacking the SCAR protein, Dictyostelium cells lacking SCAR ( scrA − cells) can still move, albeit with reduced chemoattractant-induced F-actin polymerization, presumably by employing other F-actin nucleation–promoting factors such as WASP (Blagg et al , 2003; Ibarra and Insall, 2005). On the other hand, Dictyostelium cells lacking the SCAR/WAVE complex protein PIR121 ( pirA − cells) undergo increased F-actin polymerization, enhanced pseudopod activity, and reduced substrate adhesion (Blagg et al , 2003).…”

Differential Regulation of Macropinocytosis by Abi1/Hssh3bp1 Isoforms

“…Each step of macropinocytosis, from ruffle formation to engulfment of a ruffle into a macropinosome, is likely to be regulated by multiple actin polymerization/depolymerization events [16], [17], [18]. The Abl binding protein 1 (Abi1), also known as Hssh3bp1, [19], [20], [21] is a key component of several intrinsic complexes that regulate actin cytoskeletal remodeling near the plasma membrane [22]. Overexpression of Abi1 in NIH 3T3 cells inhibits macropinocytosis [23].…”