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. 2010 Aug 15;21(16):2880-93.
doi: 10.1091/mbc.E10-04-0372. Epub 2010 Jun 23.

WASP family proteins: their evolution and its physiological implications

Douwe M Veltman  1 , Robert H Insall
Affiliations

WASP family proteins: their evolution and its physiological implications

Douwe M Veltman et al. Mol Biol Cell. .

Abstract

WASP family proteins control actin polymerization by activating the Arp2/3 complex. Several subfamilies exist, but their regulation and physiological roles are not well understood, nor is it even known if all subfamilies have been identified. Our extensive search reveals few novel WASP family proteins. The WASP, WASH, and SCAR/WAVE subfamilies are evolutionarily ancient, with WASH the most universally present, whereas WHAMM/JMY first appears in invertebrates. An unusual Dictyostelium WASP homologue that has lost the WH1 domain has retained its function in clathrin-mediated endocytosis, demonstrating that WASPs can function with a remarkably diverse domain topology. The WASH and SCAR/WAVE regulatory complexes are much more rigidly maintained; their domain topology is highly conserved, and all subunits are present or lost together, showing that the complexes are ancient and functionally interdependent. Finally, each subfamily has a distinctive C motif, indicating that this motif plays a specific role in each subfamily's function, unlike the generic V and A motifs. Our analysis identifies which features are universally conserved, and thus essential, and which are branch-specific modifications. It also shows the WASP family is more widespread and diverse than currently appreciated and unexpectedly biases the physiological role of the Arp2/3 complex toward vesicle traffic.

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Figures

Figure 1.
Figure 1.
Domain topology diagrams of WASP orthologues from unikonts, excavates, and chromalveolates. WASP is not found in plants. The regions in between the indicated domains show no sequence similarity when comparing orthologues across different kingdoms.
Figure 2.
Figure 2.
Dictyostelium WASP B and C characterization. (A) TIRF microscopy image of a Dictyostelium cell expressing GFP-tagged WASP B or C. (B) TIRF image of a Dictyostelium cell coexpressing GFP-WASP B and mRFP-clathrin light chain. (C) A time-lapse movie was recorded for a cell as shown in B. The average green and red fluorescence intensity of an area enclosing a single clathrin punctum was measured every second, and the results were plotted against time.
Figure 3.
Figure 3.
Phylogenetic tree of metazoan WASP homologues. (A) Full-length WASP protein sequences from a large number of metazoa were aligned in ClustalX, and a distance tree was calculated from the results. Bootstrap values (1000 trials) are given for the branches that separate the different colored groups. A yellow dot indicates the presence of a tandem WH2 motif at the C-terminus. Alphabetical suffixes are added for paralogues that fall within the same colored group. (B) Schematic showing the most likely sequence of events that explains the distribution of WASPs with single and tandem WH2 motifs across metazoa.
Figure 4.
Figure 4.
Domain topology diagrams of SCAR and Abi orthologues from several different organisms in each kingdom. The SCAR and Abi homology domains are defined as the largest region on the N-terminus that shows sequence similarity when comparing orthologues from different kingdoms. The regions in between indicated domains show no sequence similarity when comparing orthologues across different kingdoms.
Figure 5.
Figure 5.
The evolutionary origins of SCAR1, 2, 3, and 4. (A) Full-length SCAR protein sequences from a large number of metazoa were aligned in ClustalX, and a distance tree was calculated from the results. Bootstrap values (1000 trials) are given for the branches that separate the different colored groups. Alphabetical suffixes are added for paralogues that fall within the same colored group. (B) Schematic showing the most likely split and loss of SCAR homologues that has led to the current distribution of SCAR paralogues in vertebrates.
Figure 6.
Figure 6.
Domain topology diagrams of WASH orthologues from several organisms in each kingdom. The WASH homology domain is the largest region on the N-terminus that shows sequence similarity when comparing orthologues from different kingdoms. The regions in between domains show no sequence similarity when comparing orthologues across different kingdoms.
Figure 7.
Figure 7.
The evolutionary origins of WHAMM and JMY proteins. (A) Full-length WHAMM/JMY protein sequences from indicated organisms were aligned in ClustalX, and a distance tree was calculated from the results. Bootstrap values (1000 trials) are given for the branches that separate the different colored groups. (B) Schematic showing the most likely chronological order of the mutation of the C-terminal phenylalanine and the gene duplication of WHAMY, based on the phylogenetic tree in A. The F indicates the presence of a phenylalanine near the C-terminus, and W indicates the presence of a tryptophan at this position.
Figure 8.
Figure 8.
Domain topology diagram of metazoan WHAMM/JMY homologues. The borders of the N-terminal domain and coiled coil domain were determined by sequence alignment with WHAMM/JMY homologues where the domains have been defined.
Figure 9.
Figure 9.
Evolution of novel WASP family proteins. (A) Domain structures of four paralogues of a novel Entamoeba WASP family protein. (B) Sequence alignment of the VCA domain of the novel Entamoeba WASP family proteins. (C) Domain topology of Rattus SCAR2, SCAR3, and LOC302367. Numbers in the shaded areas indicate the percentage identity between the sequences. (D) Sequence alignment of the VCA domain of Rattus SCAR proteins and LOC302367. (E) Domain topology comparison of the divergent Rattus and Mus WASP family proteins. Numbers in the shaded areas indicate the percentage identity between the sequences.
Figure 10.
Figure 10.
Distribution of WASP family proteins across the eukaryotic tree. An evolutionary tree is drawn of the 54 organisms with completed genomes that were searched for WASP family proteins (based on Keeling et al., 2005). Branch lengths do not reflect evolutionary distances. For each organism, the presence of formins, the Arp2/3 complex and WASP family proteins is indicated with colored disks. The Arp2/3 complex was considered to be complete if subunits ArpC1-ArpC5 were present. The number of missing pie slices in some disks indicates the number of missing complex subunits. Completeness of the SCAR complex (five subunits) and the WASH complex (seven subunits) is represented in a similar manner. Footnotes for the Arp2/3 complex: (a) Incomplete ArpC4 homologue found, all other subunits are absent (b) ArpC2 and ArpC5 are absent; ArpC1 is incomplete. (c) ArpC1 and ArpC5 are absent; ArpC2, ArpC3, and ArpC4 are incomplete. The same result is obtained in the closely related Ostreococcus taurus. (d) ArpC1 and ArpC2 have substantially diverged. ArpC3 is absent.
Figure 11.
Figure 11.
VCA domain sequence alignment. VCA domain sequences from the respective WASP subfamilies of indicated organisms were aligned in ClustalX using default parameters. The shown alignment starts with the most C-terminal WH2 motif, which location is drawn in the diagram underneath the alignment. A region with high sequence similarity that is predicted to fold into an α-helix is also indicated. We define this helix as the C motif.
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