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ARP2/3 activation, WASP family proteins, WASP, WAVE, WASH, WHAMM
Abstract:
Background:
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 C-
terminal VCA domains that harbour the ARP2/3-activating regions.
Results:
To 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.
Conclusions:
Our 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.
