WAVE regulatory complex

The WAVE regulatory complex (WRC) 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.[1]

Surface model of the WAVE regulatory complex
Surface model of the WAVE regulatory holocomplex displaying all five of its components in heteropentameric form.

Composition

The proteins within the WRC form a CYFIP1-Nap1 heterodimer and a WAVE1-Abi2-HSPC300 heterotrimer,[1][2] and following interaction with Rac1, the holocomplex has been observed in a CYFIP1-Nap1-Abi2 heterotrimer subcomplex and an active WAVE1-HSPC300 heterodimer subcomplex.[3]

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.[4] The WRC is activated by interaction with the Rac1 (via the CYFIP1 component of the complex) and Arf small GTPases[1] (such as ARF1 and ARF5) or the similar protein ARL1,[2] which causes dissociation of the CYFIP1-Nap1-Abi2 heterotrimer at the membrane periphery.[3] 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.

References

  1. 1 2 3 Chen, Zhucheng; Borek, Dominika; Padrick, Shae B.; Gomez, Timothy S.; Metlagel, Zoltan; Ismail, Ayman M.; Umetani, Junko; Billadeau, Daniel D.; Otwinowski, Zbyszek; Rosen, Michael K. (25 November 2010). "Structure and control of the actin regulatory WAVE complex". Nature. 468 (7323): 533–538. PMID 21107423. doi:10.1038/nature09623.
  2. 1 2 Koronakis, V.; Hume, P. J.; Humphreys, D.; Liu, T.; Horning, O.; Jensen, O. N.; McGhie, E. J. (15 August 2011). "WAVE regulatory complex activation by cooperating GTPases Arf and Rac1". Proceedings of the National Academy of Sciences. 108 (35): 14449–14454. doi:10.1073/pnas.1107666108.
  3. 1 2 Abekhoukh, Sabiha; Bardoni, Barbara (27 March 2014). "CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome". Frontiers in Cellular Neuroscience. 8. doi:10.3389/fncel.2014.00081.
  4. ↑ Chen, Bayou; Chen, Zhucheng; Brinkmann, Klaus; Pak, Chi W.; Liao, Yuxing; Shi, Shuoyong; Henry, Lisa; Grishin, Nick V.; Bogdan, Sven; Rosen, Michael K. (16 January 2014). "The WAVE Regulatory Complex Links Diverse Receptors to the Actin Cytoskeleton". Cell. 156 (1-2): 195–207. PMID 24439376. doi:10.1016/j.cell.2013.11.048.
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