Abstract
BackgroundWASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and C-terminal VCA domains that harbour the ARP2/3-activating regions.ResultsTo reveal the evolution of ARP2/3 activation by WASP family proteins we performed a "holistic" analysis by manually assembling and annotating all homologs in most of the eukaryotic genomes available. We have identified two new families: the WAML proteins (WASP and MIM like), which combine the membrane-deforming and actin bundling functions of the IMD domains with the ARP2/3-activating VCA regions, and the WAWH protein (WASP without WH1 domain) that have been identified in amoebae, Apusozoa, and the anole lizard. Surprisingly, with one exception we did not identify any alternative splice forms for WASP family proteins, which is in strong contrast to other actin-binding proteins like Ena/VASP, MIM, or NHS proteins that share domains with WASP proteins.ConclusionsOur analysis showed that the last common ancestor of the eukaryotes must have contained a homolog of WASP, WAVE, and WASH. Specific families have subsequently been lost in many taxa like the WASPs in plants, algae, Stramenopiles, and Euglenozoa, and the WASH proteins in fungi. The WHAMM proteins are metazoa specific and have most probably been invented by the Eumetazoa. The diversity of WASP family proteins has strongly been increased by many species- and taxon-specific gene duplications and multimerisations. All data is freely accessible via http://www.cymobase.org.
Highlights
WiskottAldrich syndrome protein (WASP) family proteins stimulate the actin-nucleating activity of the ARP2/3 complex
Identification and assembly of WASP family proteins The WASP family proteins contain many but very short sequence motifs and domains. These domains are characteristic for WASP proteins but are part of proteins from other families like the WAVE homology domain (WHD) domain, that is shared by the Nance-Horan syndrome protein (NHS), the WASP homology domain 1 (WH1) domain, that is shared by the Ena/ Vasodilator-stimulated phosphoprotein (VASP) protein family, the WASP homology domain 2 (WH2) domain, that is contained for example in Spire, Cobl, missing-in-metastasis (MIM), and WASP-interacting protein (WIP), and the CA domains, that are shared for example by certain coronins and class-1 myosins
The eukaryotic genomes were analysed in an iterative search process, meaning that those genomes, for which the WASP family proteins could not unambiguously assembled in the first instance, were reanalysed as soon as further data was added to the multiple sequence alignments
Summary
WASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and Cterminal VCA domains that harbour the ARP2/3-activating regions. Signals from Rho family G-proteins activate proteins of the WASP family (WASP, WiskottAldrich syndrome protein), which stimulate the actin filament branching activity of the ARP2/3 complex [5] resulting in specialised networks of actin filaments [6,7]. The ARP2/3 complex alone is very inefficient in nucleating actin filaments but becomes activated when binding to the sites of existing actin filaments. While the WH2 domains bind G-actin the CA domains bind to and activate the ARP2/ 3 complex
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