TENASCIN-R (J1-160 180) INHIBITS FIBRONECTIN-MEDIATED CELL-ADHESION -FUNCTIONAL RELATEDNESS TO TENASCIN-C/

Cell adhesion and neurite outgrowth on fibronectin is a multistep proc ess modulated by different extra- and intracellular signals. Fibronect in-mediated cell attachment and spreading can be affected in a negativ e way by tenascin-C, an extracellular matrix glycoprotein expressed in a temporally and spacially restricted manner during early morphogenes is. Tenascin-R (J1-160/180), consisting of two major isoforms of 160 k Da (tenascin-R 160) and 180 kDa (tenascin-R 180) in mammals, is an ext racellular matrix glycoprotein of the central nervous system that shar es high structural homologies with tenascin-C. Here we show that in re lation to fibronectin-mediated adhesion, the two extracellular matrix molecules are also functionally closely related. When offered as mixed substrata with other extracellular matrix molecules, the two tenascin -R isoforms and tenascin-C derived from mouse brain selectively inhibi t fibronectin-dependent cell adhesion and neurite outgrowth, and affec t cell morphology of different mesenchymal and neural cells. This effe ct is partially due to interactions at the substrate level that result in a steric hindrance and/or conformational change of the cell bindin g sites of the fibronectin molecule. In addition, tenascin-R 180 and t enascin-C interact with cells by an RGD- and beta 1 integrin-independe nt mechanism, leading to cell rounding and detachment from such substr ata. The expression of tenascin-li and tenascin-C in the nervous syste m at times and locations where fibronectin-mediated cellular processes take place may be related to the role of inhibitory signals in the ex tracellular matrix in the regulation of cell migration and differentia tion in general.