The role of connexon aggregate fusion in gap junction growth

Gap junctions are thought to grow in size by the incorporation of single connexons and by the fusion of connexon aggregates but the relative importance of these two growth mechanisms, particularly in the formation of large gap junctions, remains unclear. We have used a quantitative approach to distinguish between these two growth mechanisms and present evidence here that gap junctions in Drosophila melanogaster wing discs have a periodic, (approximately equal to 0.025 micron 2), multimodal areal distribution which suggests that gap junctions grow by aggregate fusion. Previously published gap junction areal frequency distributions from another invertebrate, Manduca sexta, and from several vertebrate animals also show periodic (approximately equal to 0.030 micron 2), multimodal areal distributions. We suggest that the interpeak spacings on the frequency distributions represent average areas of 'unit aggregates' of connexons and that the fusion of such unit aggregates with one another and with integral multiples of unit aggregates may be a general mechanism for gap junction growth. Unit aggregates in mammals and insects are similar in surface area rather than in connexon number suggesting that a common molecular mechanism, perhaps operating at the level of the plasma membrane, may be involved in their formation and stabilization.