title: The Drosophila p21 activated kinase Mbt regulates the actin cytoskeleton and adherens junctions to control photoreceptor cell morphogenesis.
abstract: The p21 activated kinase (Pak) family of protein kinases are involved in many cellular functions like re-organisation of the cytoskeleton, transcriptional control, cell division, and survival. These pleiotropic actions are reflected in a plethora of known interacting proteins and phosphorylation substrates. Yet, the integration of a single Pak protein into signalling pathways controlling a particular developmental process are less well studied. For two of the three known Pak proteins in Drosophila melanogaster, D-Pak and Mbt, distinct functions during eye development have been established. In this study we undertook a genetic approach to identify proteins acting in the Mbt signalling pathway during photoreceptor cell morphogenesis. The genetic screen identified the actin depolymerisation factor Twinstar/Cofilin as one target of Mbt signalling. Twinstar/Cofilin becomes phosphorylated upon activation of Mbt. However, biochemical and genetic experiments question the role of the LIM domain protein kinase (Limk) as a major link between Mbt and Twinstar/Cofilin as it has been suggested for other PAK proteins. Constitutive activation of Mbt not only disturbs the actin cytoskeleton but also affects adherens junction organisation indicating a requirement of the protein in cell adhesion dependent processes during photoreceptor cell differentiation.
authors.affiliation: University of Würzburg, Institut für Medizinische Strahlenkunde und Zellforschung, Versbacherstr. 5, 97078 Würzburg, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Menzel
authors.forename: Daniela
authors.initials: D
authors.lastname: Schneeberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Raabe
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D005123:Eye / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017344:Genes, Insect; D006801:Humans; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D054462:p21-Activated Kinases
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C097180:tsr protein, Drosophila; D004247:DNA; D011494:Protein Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; C099277:Pak protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C116684:mbt protein, Drosophila; D054462:p21-Activated Kinases