Human subtelomeric WASH genes encode a new subclass of the WASP family

• Published in: PLoS genetics Vol. 3; no. 12; p. e237
• Main Authors: Linardopoulou, Elena V, Parghi, Sean S, Friedman, Cynthia, Osborn, Gregory E, Parkhurst, Susan M, Trask, Barbara J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2007; Public Library of Science (PLoS)
• Subjects: Actin-Related Protein 2-3 Complex - metabolism; Actins - metabolism; Amino Acid Sequence; Animals; Biology; Caenorhabditis; Cell Biology; Chromosomes; Chromosomes, Human - genetics; Computational Biology; Conserved Sequence; Deoxyribonucleic acid; Developmental Biology; DNA; Drosophila; Drosophila - genetics; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Entamoeba; Evolution, Molecular; Evolutionary Biology; Experiments; Gene Duplication; Gene Expression; Genes; Genes, Insect; Genetic Variation; Genetics; Genetics and Genomics; Genomes; Human; Humans; In Situ Hybridization, Fluorescence; Infectious Diseases; Insects; Molecular Biology; Molecular Sequence Data; Multigene Family; Mutation; Open Reading Frames; Pan troglodytes; Phylogeny; Primates; Primates - genetics; Proteins; Sequence Homology, Amino Acid; Signal transduction; Telomerase; Telomere - genetics; Wiskott-Aldrich Syndrome Protein Family - classification; Wiskott-Aldrich Syndrome Protein Family - genetics; Wiskott-Aldrich Syndrome Protein Family - metabolism
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.0030237

Subtelomeres are duplication-rich, structurally variable regions of the human genome situated just proximal of telomeres. We report here that the most terminally located human subtelomeric genes encode a previously unrecognized third subclass of the Wiskott-Aldrich Syndrome Protein family, whose known members reorganize the actin cytoskeleton in response to extracellular stimuli. This new subclass, which we call WASH, is evolutionarily conserved in species as diverged as Entamoeba. We demonstrate that WASH is essential in Drosophila. WASH is widely expressed in human tissues, and human WASH protein colocalizes with actin in filopodia and lamellipodia. The VCA domain of human WASH promotes actin polymerization by the Arp2/3 complex in vitro. WASH duplicated to multiple chromosomal ends during primate evolution, with highest copy number reached in humans, whose WASH repertoires vary. Thus, human subtelomeres are not genetic junkyards, and WASH's location in these dynamic regions could have advantageous as well as pathologic consequences.