CONNEXINS, CONNEXONS, AND INTERCELLULAR COMMUNICATION

Cells in tissues share ions, second messengers, and small metabolites through clusters of intercellular channels called gap junctions. This type of intercellular communication permits coordinated cellular activ ity. Intercellular channels are formed from two oligomeric integral me mbrane protein assemblies, called connexons, which span two adjacent c ells' plasma membranes and join in a narrow, extracellular ''gap.'' Co nnexons are formed from connexins, a highly related multigene family c onsisting of at least 13 members. Since the cloning of the first conne xin in 1986, considerable progress has been made in our understanding of the complex molecular switches that control the formation and perme ability of the intercellular channels. Analysis of the mechanisms of c hannel assembly has revealed the selectivity of inter-connexin interac tions and uncovered novel characteristics of the channel permeability and gating behavior. Structure-function studies provide a molecular un derstanding of the significance of connexin diversity and demonstrate the unique regulation of connexins by tyrosine kinases and oncogenes.