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, respo ...

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

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

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 compos ...

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 Cytoplasmic FMR1-interacting protein 1 is a protein that in humans is encoded by the ''CYFIP1'' gene. Interactions CYFIP1 has been shown to interact with FMR1, to the exclusion of FXR1 Fragile X mental retardation syndrome-related protein 1 is ...

ABI2 Abl interactor 2 also known as Abelson interactor 2 (Abi-2) is a protein that in humans is encoded by the ''ABI2'' gene. Interactions ABI2 has been shown to Protein-protein interaction, interact with Abl gene, ABL1, ADAM19, and TRIM32. Referen ...

, 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 In biochemistry, a protein trimer is a macromolecular complex formed by three, usually non-covalently bound, macromolecules like proteins or nucleic acids. A homotrimer would be formed by three identical molecules. A heterotrimer would be formed ...

, 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 ARF may refer to: Organizations * Advertising Research Foundation * Animal Rescue Foundation * Armenian Revolutionary Federation * ASEAN Regional Forum People * Cahit Arf (1910–1997), Turkish mathematician Science, medicine, and mathematics * ...

small GTPase Small GTPases (), also known as small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotr ...

s (such as

ARF1 ADP-ribosylation factor 1 is a protein that in humans is encoded by the ''ARF1'' gene. Function ADP-ribosylation factor 1 (ARF1) is a member of the human ARF gene family. The family members encode small guanine nucleotide-binding proteins that ...

ARF5 ADP-ribosylation factor 5 is a protein that in humans is encoded by the ''ARF5'' gene. ADP-ribosylation factor 5 (ARF5) is a member of the human ARF gene family. These genes encode small guanine nucleotide-binding proteins that stimulate the ADP- ...

, and

ARF6 ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein ...

) or the similar protein

ARL1 ADP-ribosylation factor-like protein 1 is a protein that in humans is encoded by the ''ARL1'' gene. Function The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related ...

, 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