Chapter 2: Degradation of Gap Junctions and Connexins

Abstract

Turnover and degradation of gap junctions and their constituent connexins may play an important role in the regulation of intercellular communication. Gap junction degradation is quite dynamic and can alter intercellular communication and produce distinct physiological or pathological consequences. Degradation of connexins and gap junctions must be a complicated process because gap junctions are complex structures. Gap junctions are plasma membrane structures identifiable by electron microscopy that can occupy areas as large as several square micrometers. They contain many intercellular channels that may be packed in ordered or loose arrays. A single gap junction channel consists of two hemichannels integrated into appositional plasma membranes; each hemichannel is a hexamer of subunits that are called connexins. Degradation of gap junction plaques is a complex topological problem. It is not clear a priori which proteolytic organelles would degrade the connexins. Major domains of the connexins are in the cytoplasm and would therefore be accessible to the proteasome, but their smaller extracellular domains are in a compartment that should be inaccessible to the proteasome. The extracellular domains of a connexin would be in the lumen of the lysosome after endocytosis, but interactions with the hemichannel associated with the apposed membrane might make endocytosis difficult. Whereas all connexins are similar topologically, it remains to be seen whether they are degraded by the same mechanism.