smoothened and thickveins regulate Moleskin/Importin 7-mediated MAP kinase signaling in the developing Drosophila eye.
The Drosophila Mitogen Activated Protein Kinase (MAPK) Rolled is a key regulator of developmental signaling, relaying information from the cytoplasm into the nucleus. Cytoplasmic MEK phosphorylates MAPK (pMAPK), which then dimerizes and translocates to the nucleus where it regulates transcription factors. In cell culture, MAPK nuclear translocation directly follows phosphorylation, but in developing tissues pMAPK can be held in the cytoplasm for extended periods (hours). Here, we show that Moleskin antigen (Drosophila Importin 7/Msk), a MAPK transport factor, is sequestered apically at a time when lateral inhibition is required for patterning in the developing eye. We suggest that this apical restriction of Msk limits MAPK nuclear translocation and blocks Ras pathway nuclear signaling. Ectopic expression of Msk overcomes this block and disrupts patterning. Additionally, the MAPK cytoplasmic hold is genetically dependent on the presence of Decapentaplegic (Dpp) and Hedgehog receptors.
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alysia D
AD
Vrailas
Daniel R
DR
Marenda
Summer E
SE
Cook
Maureen A
MA
Powers
James A
JA
Lorenzen
Lizabeth A
LA
Perkins
Kevin
K
Moses
D000818:Animals; D004330:Drosophila / Q000201:enzymology / Q000254:growth & development*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D005123:Eye / Q000201:enzymology / Q000254:growth & development*; D028884:Karyopherins / Q000502:physiology*; D007814:Larva / Q000201:enzymology / Q000254:growth & development; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D000072086:Smoothened Receptor
D029721:Drosophila Proteins; D028884:Karyopherins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; C100664:smo protein, Drosophila; C090169:tkv protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases