Pathways for degradation of connexins and gap junctions.
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.
Berthoud
Viviana M
VM
Department of Pediatrics, Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Ave., MC 4060, Chicago, IL 60637, USA. vberthou@peds.bsd.uchicago.edu
Minogue
Peter J
PJ
Laing
James G
JG
Beyer
Eric C
EC
D000818:Animals; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D019899:Paracrine Communication; D011480:Protease Inhibitors / Q000494:pharmacology
D017630:Connexins; D011480:Protease Inhibitors