Scribble and Discs-large direct initial assembly and positioning of adherens junctions during the establishment of apical-basal polarity

Development. 2019 Nov 21;146(22):dev180976. doi: 10.1242/dev.180976.

Abstract

Apical-basal polarity is a fundamental property of animal tissues. Drosophila embryos provide an outstanding model for defining mechanisms that initiate and maintain polarity. Polarity is initiated during cellularization, when cell-cell adherens junctions are positioned at the future boundary of apical and basolateral domains. Polarity maintenance then involves complementary and antagonistic interplay between apical and basal polarity complexes. The Scribble/Dlg module is well-known for promoting basolateral identity during polarity maintenance. Here, we report a surprising role for Scribble/Dlg in polarity initiation, placing it near the top of the network-positioning adherens junctions. Scribble and Dlg are enriched in nascent adherens junctions, are essential for adherens junction positioning and supermolecular assembly, and also play a role in basal junction assembly. We test the hypotheses for the underlying mechanisms, exploring potential effects on protein trafficking, cytoskeletal polarity or Par-1 localization/function. Our data suggest that the Scribble/Dlg module plays multiple roles in polarity initiation. Different domains of Scribble contribute to these distinct roles. Together, these data reveal novel roles for Scribble/Dlg as master scaffolds regulating assembly of distinct junctional complexes at different times and places.

Keywords: Adherens junction; Apical-basal polarity; Drosophila; Scribble.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / physiology*
  • Animals
  • Armadillo Domain Proteins / metabolism
  • Biotinylation
  • Cell Polarity / physiology*
  • Cytoskeleton / metabolism
  • Dogs
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology*
  • Ectoderm / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Gastrula / metabolism
  • Gene Expression Regulation, Developmental*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Madin Darby Canine Kidney Cells
  • Male
  • Membrane Proteins / physiology*
  • Morphogenesis
  • Mutation
  • Phenotype
  • RNA Interference
  • Shelterin Complex
  • Signal Transduction
  • Telomere-Binding Proteins / metabolism
  • Tight Junctions / metabolism
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / physiology*
  • rab5 GTP-Binding Proteins / metabolism

Substances

  • ARM protein, Drosophila
  • Armadillo Domain Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RAP1 protein, Drosophila
  • Scrib protein, Drosophila
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • baz protein, Drosophila
  • cno protein, Drosophila
  • dlg1 protein, Drosophila
  • Rab5 protein, Drosophila
  • rab5 GTP-Binding Proteins