Cardiac connexins: genes to nexus.

Abstract

Gap junctions are formed of at least 20 connexin proteins in mammals and possibly pannexins as well. Of the connexins, at least 5 (Cx30.2, Cx37, Cx40, Cx43 and Cx45) are prominently expressed in the heart and each shows regional and cell type specific expression. Contributions of each of these connexins to heart function has been in many cases illuminated by connexin null mice. The cardiac connexin genes whose genomic organization and transcriptional controls have been studied most thoroughly indicate more complex possibilities for alternate promoter usage than originally thought as well a multiple transcription factor binding sites; presumably, such complexity governs developmental timing and regional connexin expression patterns. The structure of cardiac connexin proteins indicate four primarily alpha-helical transmembrane domains, cytoplasmic amino and carboxyl termini and a cytoplasmic loop, all of which contain some regions of alpha-helix, and extracellular loops that are primarily Beta-structure. A number of proteins that bind to cardiac connexins are known, and more are certain to be discovered, linking the connexin into an intercellular signaling complex, the nexus. Binding sites may either correspond to structured regions within the connexin molecules or be unstructured, leading to presumably low-affinity and dynamic interactions.