title: WASP family proteins: their evolution and its physiological implications.
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.
authors.affiliation: Beatson Institute for Cancer Research, Glasgow, United Kingdom.
authors.forename: Douwe M
authors.initials: DM
authors.lastname: Veltman
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004023:Dictyostelium / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D049452:Green Fluorescent Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D008969:Molecular Sequence Data; D010802:Phylogeny; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D051316:Wiskott-Aldrich Syndrome Protein / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D015800:Protozoan Proteins; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family; D049452:Green Fluorescent Proteins