SWITCH IN GAP JUNCTION PROTEIN EXPRESSION IS ASSOCIATED WITH SELECTIVE CHANGES IN JUNCTIONAL PERMEABILITY DURING KERATINOCYTE DIFFERENTIATION

Gap junctional communication provides a mechanism for regulating multi cellular activities by allowing the exchange of small diffusible molec ules between neighboring cells. The diversity of gap junction proteins may exist to form channels that have different permeability propertie s. We report here that induction of terminal differentiation in mouse primary keratinocytes by calcium results in a specific switch in gap j unction protein expression. Expression of alpha(1) (connexin 43) and b eta(2) (connexin 26) gap junction proteins is down-modulated, whereas that of beta(3) (connexin 31) and beta(4) (connexin 31.1) proteins is induced. Although both proliferating and differentiating keratinocytes are electrically coupled, there are significant changes in the permea bility properties of the junctions to small molecules. In parallel wit h the changes in gap junction protein expression during differentiatio n, the intercellular transfer of the small dyes neurobiotin, carboxyfl uorescein, and Lucifer yellow is significantly reduced, whereas that o f small metabolites, such as nucleotides and amino acids, proceeds uni mpeded. Thus, a switch in gap junction protein expression in different iating keratinocytes is accompanied by selective changes in junctional permeability that may play an important role in the coordinate contro l of the differentiation process.