Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC

Development. 2020 Aug 7;147(15):dev186593. doi: 10.1242/dev.186593.

Abstract

Apical-basal polarity underpins the formation of epithelial barriers that are crucial for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. Lgl plays a role as an aPKC inhibitor, but it remains unclear whether Lgl also forms complexes with Dlg or Scrib. Using fluorescence recovery after photobleaching, we show that Lgl does not form immobile complexes at the lateral domain of Drosophila follicle cells. Optogenetic depletion of plasma membrane PIP2 or dlg mutants accelerate Lgl cortical dynamics. However, Dlg and Scrib are required only for Lgl localization and dynamic behavior in the presence of aPKC function. Furthermore, light-induced oligomerization of basolateral proteins indicates that Lgl is not part of the Scrib-Dlg complex in the follicular epithelium. Thus, Scrib and Dlg are necessary to repress aPKC activity in the lateral domain but do not provide cortical binding sites for Lgl. Our work therefore highlights that Lgl does not act in a complex but in parallel with Scrib-Dlg to antagonize apical determinants.

Keywords: Apical-basal polarity; Basolateral determinants; Dlg; Drosophila; Epithelial cell; FRAP; Lgl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Ovarian Follicle / metabolism*
  • Protein Binding
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • Scrib protein, Drosophila
  • Tumor Suppressor Proteins
  • l(2)gl protein, Drosophila
  • dlg1 protein, Drosophila
  • Protein Kinase C
  • aPKC protein, Drosophila