The WAVE regulatory complex (WRC, SCAR complex) is a five-subunit

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

complex in the Wiskott-Aldrich syndrome protein (WASP) family involved in the formation of the

actin Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...

through interaction with the

Arp2/3 complex Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton ...

. The holocomplex comprises WAVE1 (also known as WASF1), CYFIP1, ABI2, Nap1 and HSPC300 in its canonical form, or orthologues of these. WAVERegulatoryComplex

Composition

The proteins within the WRC form a CYFIP1-Nap1

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

and a WAVE1-Abi2-HSPC300 heterotrimer, and following interaction with Rac1, the holocomplex has been observed in a CYFIP1-Nap1-Abi2 heterotrimer subcomplex and an active WAVE1-HSPC300 heterodimer subcomplex.

Function

WRC recruitment to the sites of actin nucleation events at the cell periphery is mediated by the binding of a number of ligands containing a conserved WRC interacting receptor sequence (WIRS) which binds to a conserved location shared across the surfaces of Abi2 and CYFIP1. The WRC is activated by interaction with the Rac1 (via the CYFIP1 component of the complex) and Arf small GTPases (such as ARF1, ARF5, and ARF6 ) or the similar protein ARL1, which causes dissociation of the CYFIP1-Nap1-Abi2 heterotrimer at the membrane periphery. This allows the V domain of the WAVE1 component to interact with the actin monomers while its CA domain interacts with the

, allowing the Arp2/3 complex to act as a nucleation core for the branching and extension of actin filaments.

References

{{Protein-stub Protein articles without symbol Proteins