The Drosophila p21 activated kinase Mbt regulates the actin cytoskeleton and adherens junctions to control photoreceptor cell morphogenesis.
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.
Menzel
Nicolas
N
University of Würzburg, Institut für Medizinische Strahlenkunde und Zellforschung, Versbacherstr. 5, 97078 Würzburg, Germany.
Schneeberger
Daniela
D
Raabe
Thomas
T
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
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