Journal of Cell Science, Vol 110, Issue 13 1513-1522, Copyright © 1997 by Company of Biologists

JOURNAL ARTICLES

Concerted action of tenascin-C domains in cell adhesion, anti-adhesion and promotion of neurite outgrowth

D Fischer, M Brown-Ludi, T Schulthess and R Chiquet-Ehrismann
Friedrich Miescher Institute, Basel, Switzerland.

We used a new approach to identify domains of chicken tenascin-C required for interaction with cells. Instead of expressing the parts of interest, we deleted them from an otherwise intact tenascin-C molecule and scored for the concomitant change in activity. As a starting point for all mutant constructs we expressed the smallest naturally occurring tenascin-C splice variant in vertebrate cells. The tenascin-C mutants had either deletions of all EGF-like repeats, all fibronectin type III repeats or of the fibrinogen globe. In double mutants the fibronectin type III repeats were deleted together with either the EGF-like repeats or the fibrinogen globe, respectively. All tenascin-C variants assembled correctly to hexameric molecules of the expected molecular characteristics. Intact tenascin-C and the mutant missing the fibrinogen globe did not promote adhesion of chick embryo fibroblasts, whereas both, the hexamers containing solely the fibrinogen globe or the EGF-like repeats were adhesive substrates and even supported cell spreading. When tenascin-C was added to the medium of fibroblasts plated on fibronectin-coated wells, cell adhesion was blocked by intact tenascin-C, but not by mutants missing the fibrinogen globe. In neurite outgrowth assays using dorsal root ganglia, processes formed on all substrates except on the mutant missing only the fibrinogen globe, where the ganglia failed to adhere. The mutants missing the fibronectin type III repeats allowed more rapid neurite outgrowth than all other tenascin-C variants and the mutant consisting essentially of oligomerized EGF-like repeats was as active a substrate for neurite outgrowth as laminin. From the combined data, it is concluded that the activities of intact tenascin-C cannot be mimicked by investigating domain by domain, but the concerted action of several domains leads to the diverse cellular responses.

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