Cysteine residues in the cytoplasmic carboxy terminus of connexins dictate gap junction plaque stability

Mol Biol Cell. 2017 Oct 15;28(21):2757-2764. doi: 10.1091/mbc.E17-03-0206. Epub 2017 Aug 23.

Abstract

Gap junctions are cellular contact sites composed of clustered connexin transmembrane proteins that act in dual capacities as channels for direct intercellular exchange of small molecules and as structural adhesion complexes known as gap junction nexuses. Depending on the connexin isoform, the cluster of channels (the gap junction plaque) can be stably or fluidly arranged. Here we used confocal microscopy and mutational analysis to identify the residues within the connexin proteins that determine gap junction plaque stability. We found that stability is altered by changing redox balance using a reducing agent-indicating gap junction nexus stability is modifiable. Stability of the arrangement of connexins is thought to regulate intercellular communication by establishing an ordered supramolecular platform. By identifying the residues that establish plaque stability, these studies lay the groundwork for exploration of mechanisms by which gap junction nexus stability modulates intercellular communication.

MeSH terms

  • Animals
  • Cell Communication / physiology
  • Cell Line
  • Connexins / metabolism*
  • Connexins / physiology
  • Cysteine / metabolism
  • Cytoplasm
  • Cytosol / metabolism
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism
  • Gap Junctions / metabolism*
  • Gap Junctions / physiology
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Protein Domains
  • Protein Isoforms
  • Rats

Substances

  • Connexins
  • Membrane Proteins
  • Protein Isoforms
  • Cysteine