Gap junctions – from cell to molecule

Gap junctions were first defined morphologically as specialized contacts between cells that mediate the direct exchange of small molecules needed to coordinate behavior of multicellular systems. As a functional entity, they have evolved independently three times, if one includes plasmodesmata in plants, which are structurally very distinct from gap junctions but mediate similar functions. The gap junctions of vertebrates and invertebrates are similar in both structure and function, but the former are composed of the connexin family (Eiberger et al., 2001; Willecke et al., 2002), while the latter are composed of members of a topologically similar but unrelated family called the innexins (Phelan and Starrich, 2001). Recently, however, three ‘pannexin ’ genes displaying distant homology to the innexins, but of as yet unknown function, have been found in vertebrates (Panchin et al., 2000). Diverse functions The ubiquitous presence of gap junctions in the metazoa has suggested that they are essential for multicellular life – a conclusion that is supported by the array of different human diseases and mouse phenotypes that arise from defects in these genes. Some of the diseases have a significant impact on the human population, with Cx26 mutations accounting for over 50 % of the cases of inherited asymptomatic sensoneural deafness (Kelsell et al., 1997). Among the phenotypic consequences of connexin loss, some appear to reflect the role of gap junctions as ion conductors, such as the loss of retinal rod signaling, cortical asynchrony (Cx36), partial conductance block (Cx40) and ventricular arrhythmias (Cx43) in the heart, and K + recycling in the ear (Cx26 and Cx30). Others are likely to result from interruption of nutrient transfer between cells, as in the avascular eye lens (Cx46 and Cx50) and placental transfer to the fetus (Cx26 and Cx31). Yet other defects illustrate the probable role of gap junctions in mediating intercellular signaling, such as coordination of neural