title: Su(dx) E3 ubiquitin ligase-dependent and -independent functions of polychaetoid, the Drosophila ZO-1 homologue.
abstract: Zona occludens (ZO) proteins are molecular scaffolds localized to cell junctions, which regulate epithelial integrity in mammals. Using newly generated null alleles, we demonstrate that polychaetoid (pyd), the unique Drosophila melanogaster ZO homologue, regulates accumulation of adherens junction-localized receptors, such as Notch, although it is dispensable for epithelial polarization. Pyd positively regulates Notch signaling during sensory organ development but acts negatively on Notch to restrict the ovary germline stem cell niche. In both contexts, we identify a core antagonistic interaction between Pyd and the WW domain E3 ubiquitin ligase Su(dx). Pyd binds Su(dx) directly, in part through a noncanonical WW-binding motif. Pyd also restricts epithelial wing cell numbers to control adult wing shape, a function associated with the FERM protein Expanded and independent of Su(dx). As both Su(dx) and Expanded regulate trafficking, we propose that a conserved role of ZO proteins is to coordinate receptor trafficking and signaling with junctional organization.
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, England, UK.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Djiane
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Marian
authors.initials: M
authors.lastname: Wilkin
authors.forename: Sabine
authors.initials: S
authors.lastname: Mazleyrat
authors.forename: Martin D
authors.initials: MD
authors.lastname: Jennings
authors.forename: Johanna
authors.initials: J
authors.lastname: Avis
authors.forename: Sarah
authors.initials: S
authors.lastname: Bray
authors.forename: Martin
authors.initials: M
authors.lastname: Baron
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000483:Alleles; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D005260:Female; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010053:Ovary / Q000166:cytology; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch / Q000378:metabolism; D012679:Sense Organs / Q000166:cytology / Q000196:embryology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013329:Structure-Activity Relationship; D062725:Tight Junction Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014921:Wings, Animal / Q000033:anatomy & histology / Q000166:cytology / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D051880:Receptors, Notch; D062725:Tight Junction Proteins; D062826:Zonula Occludens-1 Protein; C569041:pyd protein, Drosophila; D011392:Proline; C119838:Su(dx) protein, Drosophila; D044767:Ubiquitin-Protein Ligases