Biogenesis and degradation of gap junctions

The dynamic regulation of gap junction biogenesis and degradation is a key element in the control of intercellular communication. This regulation starts in the endoplasmic reticulum, in which a large fraction of newly synthesized connexin molecules can be degraded. Multisubunit assembly of endogenously expressed connexins is first detected in the trans-Golgi network, as opposed to the endoplasmic reticulum wherein most other integral membrane proteins oligomerize. Gap junction plaques grow, at least in part, by lateral diffusion of plasma membrane connexin hemichannels to the periphery of the plaques. Connexins have a half-life of a few hours, being turned over within the endoplasmic reticulum by the ubiquitin/proteasome system and after transport to the cell surface via the lysosome. Although some aspects of gap junction biogenesis and degradation are relatively well understood, several intriguing unanswered questions remain.