WAVE regulatory complex
The WAVE regulatory complex (WRC, SCAR complex) is a five-subunit protein complex in the Wiskott-Aldrich syndrome protein (WASP) family involved in the formation of the actin cytoskeleton through interaction with the Arp2/3 complex. The holocomplex comprises WAVE1 (also known as WASF1), CYFIP1, ABI2, Nap1 and HSPC300 in its canonical form, or orthologues of these.{{cite journal | vauthors = Chen Z, Borek D, Padrick SB, Gomez TS, Metlagel Z, Ismail AM, Umetani J, Billadeau DD, Otwinowski Z, Rosen MK | title = Structure and control of the actin regulatory WAVE complex | journal = Nature | volume = 468 | issue = 7323 | pages = 533–8 | date = November 2010 | pmid = 21107423 | pmc = 3085272 | doi = 10.1038/nature09623 | bibcode = 2010Natur.468..533C }}
Composition
The proteins within the WRC form a CYFIP1-Nap1 heterodimer and a WAVE1-Abi2-HSPC300 heterotrimer,{{cite journal | vauthors = Koronakis V, Hume PJ, Humphreys D, Liu T, Hørning O, Jensen ON, McGhie EJ | title = WAVE regulatory complex activation by cooperating GTPases Arf and Rac1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 35 | pages = 14449–54 | date = August 2011 | pmid = 21844371 | pmc = 3167530 | doi = 10.1073/pnas.1107666108 | bibcode = 2011PNAS..10814449K | doi-access = free }} and following interaction with Rac1, the holocomplex has been observed in a CYFIP1-Nap1-Abi2 heterotrimer subcomplex and an active WAVE1-HSPC300 heterodimer subcomplex.{{cite journal | vauthors = Abekhoukh S, Bardoni B | title = CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 81 | date = 27 March 2014 | pmid = 24733999 | doi = 10.3389/fncel.2014.00081 | pmc = 3973919 | doi-access = free }}
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.{{cite journal | vauthors = Chen B, Brinkmann K, Chen Z, Pak CW, Liao Y, Shi S, Henry L, Grishin NV, Bogdan S, Rosen MK | title = The WAVE regulatory complex links diverse receptors to the actin cytoskeleton | journal = Cell | volume = 156 | issue = 1–2 | pages = 195–207 | date = January 2014 | pmid = 24439376 | doi = 10.1016/j.cell.2013.11.048 | pmc = 4059610 }} 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{{cite journal | vauthors = Humphreys D, Davidson AC, Hume PJ, Makin LE, Koronakis V | title = Arf6 coordinates actin assembly through the WAVE complex, a mechanism usurped by Salmonella to invade host cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 42 | pages = 16880–5 | date = October 2013 | pmid = 24085844 | pmc = 3801044 | doi = 10.1073/pnas.1311680110 | bibcode = 2013PNAS..11016880H | doi-access = free }} ) 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 Arp2/3 complex, allowing the Arp2/3 complex to act as a nucleation core for the branching and extension of actin filaments.