title: Polarized subcellular localization of Jak/STAT components is required for efficient signaling.
abstract: Three protein complexes control polarization of epithelial cells: the apicolateral Crumbs and Par-3 complexes and the basolateral Lethal giant larvae complex. Polarization results in the specific localization of proteins and lipids to different membrane domains. The receptors of the Notch, Hedgehog, and WNT pathways are among the proteins that are polarized, with subcellular receptor localization representing an important aspect of signaling regulation. For example, in the WNT pathway, differential DFz2 receptor localization results in activation of either the canonical or the planar polarity pathway. Despite the large body of research on the vertebrate JAK/STAT pathway, there are no reports indicating polarized signaling. By using the conserved Drosophila JAK/STAT pathway as a system, we find that the receptor and its associated kinase are located in the apical membrane of epithelial cells. Unexpectedly, the transcription factor STAT is enriched in the apicolateral membrane domain of ectoderm epithelial cells in a Par-3-dependent manner. Our results indicate that preassembly of STAT and the Receptor/JAK complex to specific membrane domains is a key aspect for signaling efficiency. Our results also suggest that receptor polarization in the ectoderm cell membrane restricts the cell's response to ligands provided by neighboring cells.
authors.affiliation: CABD-CSIC, Universidad Pablo de Olavide, 41013 Sevilla, Spain. ssotmar@upo.es
authors.forename: Sol
authors.initials: S
authors.lastname: Sotillos
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Díaz-Meco
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
authors.forename: James
authors.initials: J
authors.lastname: Castelli-Gair Hombría
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D004475:Ectoderm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases