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Vol. 8, Issue 10, 2055-2075, October 1997

§
*Friedrich-Miescher Institut, CH-4002 Basel, Switzerland;
Tenascin-C is an adhesion-modulating matrix glycoprotein
that has multiple effects on cell behavior. Tenascin-C transcripts are
expressed in motile cells and at sites of tissue modeling during
development, and alternative splicing generates variants that encode
different numbers of fibronectin type III repeats. We have examined the
in vivo expression and cell adhesive properties of two
full-length recombinant tenascin-C proteins: TN-190, which contains the
eight constant fibronectin type III repeats, and TN-ADC, which contains
the additional AD2, AD1, and C repeats. In situ hybridization with
probes specific for the AD2, AD1, and C repeats shows that these splice
variants are expressed at sites of active tissue modeling and
fibronectin expression in the developing avian feather bud and sternum.
Transcripts incorporating the AD2, AD1, and C repeats are present in
embryonic day 10 wing bud but not in embryonic day 10 lung. By using a
panel of nine cell lines in attachment assays, we have found that
C2C12, G8, and S27 myoblastic cells undergo concentration-dependent
adhesion to both variants, organize actin microspikes that contain the
actin-bundling protein fascin, and do not assemble focal contacts. On a
molar basis, TN-ADC is more active than TN-190 in promoting cell
attachment and irregular cell spreading. The addition of either TN-190
or TN-ADC in solution to C2C12, COS-7, or MG-63 cells adherent on fibronectin decreases cell attachment and results in decreased organization of actin microfilament bundles, with formation of cortical
membrane ruffles and retention of residual points of substratum contact
that contain filamentous actin and fascin. These data establish a
biochemical similarity in the processes of cell adhesion to tenascin-C
and thrombospondin-1, also an "antiadhesive" matrix component, and
also demonstrate that both the adhesive and adhesion-modulating
properties of tenascin-C involve similar biochemical events in the
cortical cytoskeleton. In addition to these generic properties, TN-ADC
is less active in adhesion modulation than TN-190. The coordinated
expression of different tenascin-C transcripts during development may,
therefore, provide appropriate microenvironments for regulated changes
in cell shape, adhesion, and movement.
Department of Cell Biology and Human Anatomy, School of
Medicine, University of California, Davis, California 95616-8643; and
MRC-1, Laboratory for Molecular Cell Biology and
Department of Biochemistry and Molecular Biology, University College
London, London WC1E 6BT, United Kingdom
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