Pathways for degradation of connexins and gap junctions

Cardiovasc Res. 2004 May 1;62(2):256-67. doi: 10.1016/j.cardiores.2003.12.021.


Gap junctional proteins, connexins, and gap junctional plaques are short-lived. Three pathways for their degradation have been proposed: (1) misfolded/abnormally oligomerized connexins are retrogradely translocated and degraded by the proteasome through endoplasmic reticulum-associated degradation; (2) connexins (as monomers or oligomers) may traffic directly from an early secretory compartment to the lysosome for degradation without reaching the plasma membrane; (3) connexins within gap junction plaques are degraded by the lysosome after endocytotic internalization. Degradation of gap junction plaques is proteasome-dependent in some cell types. Degradation may be regulated by ubiquitinylation, phosphorylation, or polypeptide domains that act as sorting signals.

Publication types

  • Review

MeSH terms

  • Animals
  • Connexins / metabolism*
  • Gap Junctions / metabolism*
  • Half-Life
  • Humans
  • Lysosomes / metabolism
  • Models, Biological
  • Paracrine Communication*
  • Protease Inhibitors / pharmacology


  • Connexins
  • Protease Inhibitors