The Connexin Turnover, an Important Modulating Factor of the Level of Cell-to-cell Junctional Communication: Comparison with Other Integral Membrane Proteins

The constituent proteins of gap junctions, called "connexins" (Cxs) in chordates, are generally renewed several times a day, in approximately the same rate range as many other integral plasma membrane proteins and the proteins of other channels, other intercellular junctions or different membrane receptors. This permanent renewal turns on a fine-tuned balance among various processes, such as gene transcription, mRNA stability and processing, protein synthesis and oligomerization, posttranslational modifications, transport to the plasma membrane, anchoring to the cytoskeleton, connexon aggregation and docking, regulation of endocytosis and controlled degradations of the proteins. Subtle changes at one or some of these steps would represent an exquisite level of regulation that extends beyond the rapid channel opening and closure events associated with channel gating; membrane channels and receptors are constantly able to answer to physiological requirements to either up- or downregulate their activity. The Cx turnover rate thereby appears to be a key component in the regulation of any protein, particularly of gap junctional proteins. However, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation remain poorly understood.