Dystroglycan and perlecan provide a basal cue required for epithelial polarity during energetic stress

Dev Cell. 2009 Jan;16(1):83-92. doi: 10.1016/j.devcel.2008.11.006.

Abstract

Dystroglycan localizes to the basal domain of epithelial cells and has been reported to play a role in apical-basal polarity. Here, we show that Dystroglycan null mutant follicle cells have normal apical-basal polarity, but lose the planar polarity of their basal actin stress fibers, a phenotype it shares with Dystrophin mutants. However, unlike Dystrophin mutants, mutants in Dystroglycan or in its extracellular matrix ligand Perlecan lose polarity under energetic stress. The maintenance of epithelial polarity under energetic stress requires the activation of Myosin II by the cellular energy sensor AMPK. Starved Dystroglycan or Perlecan null cells activate AMPK normally, but do not activate Myosin II. Thus, Perlecan signaling through Dystroglycan may determine where Myosin II can be activated by AMPK, thereby providing the basal polarity cue for the low-energy epithelial polarity pathway. Since Dystroglycan is often downregulated in tumors, loss of this pathway may play a role in cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Cell Polarity / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / physiology
  • Dystroglycans / genetics
  • Dystroglycans / metabolism*
  • Epithelial Cells* / cytology
  • Epithelial Cells* / metabolism
  • Female
  • Heparan Sulfate Proteoglycans / genetics
  • Heparan Sulfate Proteoglycans / metabolism*
  • Humans
  • Male
  • Myosin Type II / metabolism
  • Oocytes / cytology
  • Oocytes / physiology
  • Ovarian Follicle / cytology
  • Ovarian Follicle / metabolism
  • Phenotype
  • Signal Transduction / physiology*
  • Stress Fibers / metabolism
  • Stress, Physiological*

Substances

  • Drosophila Proteins
  • Heparan Sulfate Proteoglycans
  • perlecan
  • Dystroglycans
  • AMP-Activated Protein Kinases
  • Myosin Type II