Autophagy: a pathway that contributes to connexin degradation

J Cell Sci. 2011 Mar 15;124(Pt 6):910-20. doi: 10.1242/jcs.073072.

Abstract

The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytoplasmic connexins were partially (cup-shaped) or completely (ring-shaped) enclosed by structures containing the autophagy-related protein LC3. Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. These results demonstrate that autophagy can regulate cellular levels of wild-type connexins and imply that the persistence of accumulations of CX50P88S results from insufficient degradation capacity of constitutive autophagy.

Publication types

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

MeSH terms

  • Animals
  • Autophagy*
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Connexins / genetics
  • Connexins / metabolism*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Protein Transport

Substances

  • Connexin 43
  • Connexins
  • Eye Proteins
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • connexin 50