A neural-specific splicing event generates an active form of the Wiskott-Aldrich syndrome protein.
Actin polymerization is required for cellular events such as podosome, lamellipode or filopode formation in migrating cells, and members of the Wiskott-Aldrich syndrome protein (WASP) family have essential roles in regulating actin dynamics at the cell leading edge. However, WASP proteins need first to be activated in order to be able to target actin polymerization. Here, we show the occurrence of a neural-specific splicing event, which is favoured by the nuclear orphan receptor chicken ovalbumin upstream promoter-transcription factor I, and generates a truncated WASP protein deleted of exon 2-encoded amino acids. This deletion relocates the protein to the plasma membrane and induces the formation of actin-rich podosome-like structures that also contain paxillin and vinculin. Furthermore, expression of the truncated protein in PC12 cells, as well as in primary neurons, stimulates neuritogenesis. These data underscore the importance of the neural-specific splicing of WASP RNA during development.
Le Page
Yann
Y
Equipe 'Information et Programmation Cellulaire', UMR 6026 CNRS, Université de Rennes I, Campus de Beaulieu, 35042 Rennes Cedex, France.
Demay
Florence
F
Salbert
Gilles
G
D000199:Actins / Q000378:metabolism; D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D051838:COUP Transcription Factor I; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D005091:Exons / Q000502:physiology; D017930:Genes, Reporter; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497591:Nr2f1 protein, rat; D020033:Protein Isoforms; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C495769:Was protein, rat; D051316:Wiskott-Aldrich Syndrome Protein