Evidence for a nuclear role for Drosophila Dlg as a regulator of the NURF complex

Mol Biol Cell. 2021 Nov 1;32(21):ar23. doi: 10.1091/mbc.E21-04-0187. Epub 2021 Sep 8.

Abstract

Scribble (Scrib), Discs-large (Dlg), and Lethal giant larvae (Lgl) are basolateral regulators of epithelial polarity and tumor suppressors whose molecular mechanisms of action remain unclear. We used proximity biotinylation to identify proteins localized near Dlg in the Drosophila wing imaginal disc epithelium. In addition to expected membrane- and cytoskeleton-associated protein classes, nuclear proteins were prevalent in the resulting mass spectrometry dataset, including all four members of the nucleosome remodeling factor (NURF) chromatin remodeling complex. Subcellular fractionation demonstrated a nuclear pool of Dlg and proximity ligation confirmed its position near the NURF complex. Genetic analysis showed that NURF activity is also required for the overgrowth of dlg tumors, and this growth suppression correlated with a reduction in Hippo pathway gene expression. Together, these data suggest a nuclear role for Dlg in regulating chromatin and transcription through a more direct mechanism than previously thought.

Publication types

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

MeSH terms

  • Animals
  • Cell Polarity / genetics
  • Cytoskeletal Proteins / metabolism
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Drosophila melanogaster
  • Epithelial Cells / metabolism
  • Epithelium
  • Imaginal Discs / metabolism
  • Membrane Proteins / metabolism
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Nuclear Proteins / metabolism
  • Protein Kinase C / metabolism
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / physiology

Substances

  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Scrib protein, Drosophila
  • Transcription Factors
  • Tumor Suppressor Proteins
  • l(2)gl protein, Drosophila
  • dlg1 protein, Drosophila
  • Protein Kinase C
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex