Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat.
The Drosophila genes fat (ft) and dachsous (ds) encode large atypical cadherins that collaborate to coordinately polarize cells in the plane of the epithelium (planar cell polarity) and to affect growth via the Warts/Hippo pathway. Ft and Ds form heterodimeric bridges that convey polarity information from cell to cell. four-jointed (fj) is a modulator of Ft/Ds activity that acts in a graded fashion in the abdomen, eye, and wing. Genetic evidence indicates that Fj acts via Ds and/or Ft, and here we demonstrate that Fj can act independently on Ds and on Ft. It has been reported that Fj has kinase activity and can phosphorylate a subset of cadherin domains of both Ft and Ds in vitro. We have used both cell and in vitro assays to measure binding between Ft and Ds. We find that phosphorylation of Ds reduces its affinity for Ft in both of these assays. By expressing forms of Ds that lack the defined phosphorylation sites or have phosphomimetic amino acids at these positions, we demonstrate that effects of Fj on wing size and planar polarity can be explained by Fj phosphorylating these sites.
Brittle
Amy L
AL
Medical Research Council (MRC) Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Repiso
Ada
A
Casal
José
J
Lawrence
Peter A
PA
Strutt
David
D
D000818:Animals; D001665:Binding Sites / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D050437:Genes, Developmental / Q000235:genetics* / Q000502:physiology; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D014921:Wings, Animal / Q000254:growth & development
D015820:Cadherins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; C094449:ds protein, Drosophila; C095900:fj protein, Drosophila; C472307:ft protein, Drosophila