31 - Biology of Gap Junctions

Abstract

This chapter discusses biology of gap junctions. Gap junction can be defined as a structure serving as an electrical synapse in excitable tissues and as permeable cell-to-cell ion channels in inexcitable cells. The chapter discusses several concepts related to gap junctions, including advantages of electrical synapses in excitable cells, ubiquitous membrane permeable junctions, structural candidates for the permeable cell junction, ultrastructural characterization and correlations with cell coupling, molecular and structural studies of gap junction proteins, and two large families of gap junction proteins. Gap junctions in human disease and in murine models of human disease further discuss arcinogenesis, Charcot-Marie-tooth disease and mutations of Cx32, heart function and mutations of Cx43 and Cx40, cataract formation and mutations of Cx50, deafness and mutations of Cx26 and, fertility and targeted knockout of Cx37. Developmental studies now seem to hold particular promise, while studies in the field of cancer cell biology continue to make progress, including analysis of the relationship between connexin expression, processing, assembly, gating, and degradation and transformation to malignancy. Current studies of the properties of gap junction channels and of the cellular regulation of gap junction gating, formation, and turnover in relation to normal cell physiology may yield more specific functional information. Connexin-specific gap junction channels exhibit differences in electrical conductance and molecular permeability that are not directly correlated and dispute the contention that all gap junctions are large aqueous pores. DNAs encoding several connexins have been cloned and significant advances have been made in the correlation of sequence and function. The application of this knowledge to the development of transgenic animals exhibiting gain or loss of function of specific connexins continue to lead to more specific insights into the functional significance of particular connexins and innexins. In conclusion, it is unlikely that the progression of all cancers is dependent upon the activity of gap junctions. It is also unlikely that mechanisms of gap junction-mediated growth control will be identical in all cells or tumors where the activity of gap junctions can be demonstrated to play a pivotal role.