Life cycle of connexins: regulation of connexin synthesis and degradation.

Gap-junction-forming connexins (Cx) exhibit a complex life cycle which is regulated at various levels. First, the promoter regions and binding of transcription factors to them control the transcription of the connexin genes. Translation of Cx-mRNA seems to be enabled by internal ribosome entry site elements allowing translation even under stress conditions. The newly synthetized Cx protein (monomeric) is transferred to the Golgi apparatus, oligomerized, transferred to the plasma membrane and incorporated into gap junction plaques. Two principal pathways for degradation of Cx could be defined: (a) lysosomal and (b) proteasomal degradation, including phosphorylation and ubiquitination as well as the internalization of complete gap junction channels as annular gap junctions doomed to degradation. In the present article, the various steps of the life cycle of cardiac connexins and its regulation are reviewed.