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 process modulated by different extra- and intracellular signals. Fibronectin-mediated cell attachment and spreading can be affected in a negative way by tenascin-C, an extracellular matrix glycoprotein expressed in a temporally and spacially restricted manner during early morphogenesis. Tenascin-R (J1-160/180), consisting of two major isoforms of 160 kDa (tenascin-R 160) and 180 kDa (tenascin-R 180) in mammals, is an extracellular matrix glycoprotein of the central nervous system that shares high structural homologies with tenascin-C. Here we show that in relation 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 inhibit fibronectin-dependent cell adhesion and neurite outgrowth, and affect cell morphology of different mesenchymal and neural cells. This effect is partially due to interactions at the substrate level that result in a steric hindrance and/or conformational change of the cell binding sites of the fibronectin molecule. In addition, tenascin-R 180 and tenascin-C interact with cells by an RGD- and beta 1 integrin-independent mechanism, leading to cell rounding and detachment from such substrata. The expression of tenascin-R and tenascin-C in the nervous system at times and locations where fibronectin-mediated cellular processes take place may be related to the role of inhibitory signals in the extracellular matrix in the regulation of cell migration and differentiation in general.
Pesheva
P
P
Department of Neurobiology, Swiss Federal Institute of Technology, Zürich.
Probstmeier
R
R
Skubitz
A P
AP
McCarthy
J B
JB
Furcht
L T
LT
Schachner
M
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology*; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007739:L Cells; D051379:Mice; D016501:Neurites / Q000187:drug effects*; D011946:Receptors, Antigen / Q000378:metabolism; D019063:Tenascin
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011946:Receptors, Antigen; D019063:Tenascin; C028641:Tn receptor; C074638:tenascin R