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WASP family proteins: their evolution and its physiological implications.

Veltman DM, Insall RH - Mol. Biol. Cell (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beatson Institute for Cancer Research, Glasgow, United Kingdom.

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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Related in: MedlinePlus

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.
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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.

Mentions: In Entamoeba, our search yielded four novel proteins with a C-terminal VCA domain. The proteins are highly homologous to each other over their entire sequence, clearly identifying them as paralogues. Their general domain topology is comparable to that of known WASP family members (Figure 9A), having an N-terminal homology region, followed by a poorly conserved linker region, a poly-proline region, and a C-terminal VCA domain. The VCA domain is very similar to that of known WASP family members; the WH2 motif, the C motif, and acidic region are all present, and the spacing between the regions is similar compared with the VCA domains of WASP or SCAR (Figure 9B). However, the N-terminal domain of these proteins has no sequence similarity with any of the known WASP family members. Instead, the N-terminal domain is most similar to the I-BAR domain (Habermann, 2004). In fact, these novel WASP family proteins are also identified by BLAST searching with the I-BAR domain of Dictyostelium IRSp53/IRTKS [DictyBase:DDB_G0274805]. I-BAR domain–containing adapter proteins such as IRSp53 and IRTKS couple membrane dynamics to actin polymerization by means of a C-terminal SH3 domain (Scita et al., 2008). These novel Entamoeba WASP family proteins may have cut such a pathway short by directly coupling the I-BAR domain to a VCA domain.


WASP family proteins: their evolution and its physiological implications.

Veltman DM, Insall RH - Mol. Biol. Cell (2010)

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.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2921111&req=5

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.
Mentions: In Entamoeba, our search yielded four novel proteins with a C-terminal VCA domain. The proteins are highly homologous to each other over their entire sequence, clearly identifying them as paralogues. Their general domain topology is comparable to that of known WASP family members (Figure 9A), having an N-terminal homology region, followed by a poorly conserved linker region, a poly-proline region, and a C-terminal VCA domain. The VCA domain is very similar to that of known WASP family members; the WH2 motif, the C motif, and acidic region are all present, and the spacing between the regions is similar compared with the VCA domains of WASP or SCAR (Figure 9B). However, the N-terminal domain of these proteins has no sequence similarity with any of the known WASP family members. Instead, the N-terminal domain is most similar to the I-BAR domain (Habermann, 2004). In fact, these novel WASP family proteins are also identified by BLAST searching with the I-BAR domain of Dictyostelium IRSp53/IRTKS [DictyBase:DDB_G0274805]. I-BAR domain–containing adapter proteins such as IRSp53 and IRTKS couple membrane dynamics to actin polymerization by means of a C-terminal SH3 domain (Scita et al., 2008). These novel Entamoeba WASP family proteins may have cut such a pathway short by directly coupling the I-BAR domain to a VCA domain.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Beatson Institute for Cancer Research, Glasgow, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus