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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actins / metabolism
-
Adherens Junctions / metabolism
-
Animals
-
Animals, Genetically Modified
-
Base Sequence
-
Cell Differentiation
-
Cell Line
-
Cytoskeleton / metabolism
-
DNA / genetics
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Drosophila melanogaster / cytology
-
Drosophila melanogaster / genetics
-
Drosophila melanogaster / growth & development*
-
Drosophila melanogaster / metabolism*
-
Eye / cytology
-
Eye / growth & development
-
Eye / metabolism
-
Genes, Insect
-
Humans
-
Lim Kinases
-
Microfilament Proteins / genetics
-
Microfilament Proteins / metabolism
-
Microscopy, Electron, Scanning
-
Mutagenesis, Site-Directed
-
Mutation
-
Phenotype
-
Phosphorylation
-
Photoreceptor Cells, Invertebrate / cytology
-
Photoreceptor Cells, Invertebrate / growth & development
-
Photoreceptor Cells, Invertebrate / metabolism*
-
Protein Kinases / genetics
-
Protein Kinases / metabolism*
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism
-
Recombinant Proteins / genetics
-
Recombinant Proteins / metabolism
-
Signal Transduction
-
Transfection
-
p21-Activated Kinases
Substances
-
Actins
-
Drosophila Proteins
-
Microfilament Proteins
-
Recombinant Proteins
-
tsr protein, Drosophila
-
DNA
-
Protein Kinases
-
LIMK1 protein, human
-
Lim Kinases
-
Pak protein, Drosophila
-
Protein Serine-Threonine Kinases
-
mbt protein, Drosophila
-
p21-Activated Kinases