Gap Junction-mediated Intercellular Signalling in Health and Disease

The protein structural component of gap junctions is the connexin. Studies onthe association properties of the connexins to form heteromeric connexons andheterotypic gap junctions are necessary for a complete understanding of the role ofdifferent connexins in gap junction function. The connexins are coded by a multigenefamily consisting of at least 16 members. Most cells express multiple types of connexinthat can potentially associate to form gap junction channels containing more than onetype of connexin. The permeability and gating characteristics of gap junction channelsare dependent on the isoform and post-translational modifications present on theconnexins and their association properties. Together with an observed selectivity in theassociation properties of the different connexins and the development of more specificperturbation approaches, these studies have provided insights into the significance ofconnexin diversity and the temporal expression patterns for connexins that have beendeterminedin viva in both developmental and differentiating systems. 1999 Gap junction-mediated intercellular signalling in bealfh and disease. WiLiley, Chichester(Novartis Foundation Symposium 2 19) p 6-2 I It has been more than 30 years since the presence of a low resistance electricalpathway between adjacent crayfish axons was first described (Furshpan & Potter1959). This was followed by the finding that these same pathways also existed innon-excitable cells, and that they allowed the passage of larger hydrophilicmolecules without leakage into the extracellular space. These observationssuggested that the channel responsible for these pathways must exist between thetwo cell membranes and be continuous. The membrane differentiation that wasimplicated in this pathway was ultimately identified as the gap junction. Connexin multigene family The gap junction was first clearly observed in its present form by electronmicroscopy as a septalaminar structure with a2-4 nm space or ‘gap’ between twoopposing cells. In enface views, a polygonal lattice of about 7.5 A subunits could be