DIFFERENTIAL REGULATION OF COMMUNICATION BY RETINOIC ACID IN HOMOLOGOUS AND HETEROLOGOUS JUNCTIONS BETWEEN NORMAL AND TRANSFORMED-CELLS

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 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 (greater-than-or-equal-to 10(-9) M) and its benzoic acid derivative tetrahydrotetramethylnaphthalenylpropenylbenzoic acid (greater-than-or-equal-to 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.