The permeability of junctions between cells of the same type (homologous junctions) is greatly increased by retinoic acid (10-9-10-8 M), a probable morphogen, and this responsiveness is shared by a variety of normal and transformed cell types (Mehta, P. P., J. S. Bertram, and W. R. Loewenstein. 1989. J. Cell Biol. 108:1053-1065). Here we report that the heterologous junctions between the normal and transformed cells respond in the opposite direction; their permeability is reduced by retinoic acid (≥10-9 M) and (its benzoic acid derivative tetrahydrotetramethylnaph-thalenylpropenylbenzoic acid (≥10-11 M). The opposite responses of the two classes of junction are shown to be concurrent; in cocultures of normal 10T1/2 cells and their methylcholanthrene-transformed counterparts, the permeability of the heterologous junctions, which is lower than that of the homologous junctions to start with, falls (within 20 h of retinoid application), at the same time that the permeability of the homologous junctions rises in both cell types. Such a counter-regulation requires a minimum of three degrees of cellular differentiation. A model is proposed in which the differentiations reside in a trio of junctional channel protein. The principle of the model may have wide applications in the regulation of intercellular communication at tissue boundaries, including embryonic ones.
ASJC Scopus subject areas
- Cell Biology