Learning the language of cell-cell communication through connexin channels

Abstract

Researchers working in the field of gap junctions, the membrane structures dedicated to direct cell-cell communication, might have felt, at times, as if they are children of a lesser god. The molecular cloning of connexins and their identification as the protein components of gap junctions heralded a new era, but compared to the progress achieved in deciphering other junctional structures, it looked as though cadherin and integrins were sprinting in a fast lane and leaving gap junctions behind. But gap junctions are not simple structures of contact between cells, they are in fact channels formed by the oligomerization of connexins: six connexins make a connexon or hemichannel, and two connexons from adjacent cells align in the extracellular space to make a full intercellular gap junction channel that allows direct communication between cells without using the extracellular space to exchange messages. Compared to classical ion channels, however, studies of intercellular ones have suffered from the lack of clear ionic selectivity and of specific toxins to probe their function. But if these aspects led to a grim mood among researchers, it has disappeared with the discovery that several genetic diseases are linked to mutations in connexin genes. The recent meeting on connexins and gap junctions, attended by the vast majority of people active in the field, confirmed some of the trends that have emerged and that are allowing us to make sense of the complexity of connexin language, and announced some of the new avenues that are beginning to be explored.