Molecules in focus
Tenascins

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Abstract

Tenascins are a family of large multimeric extracellular matrix (ECM) proteins. Vertebrates express four tenascins termed tenascin-C, -R, -X and -W present in their connective tissues. Each tenascin has a specific expression pattern. To the contrary of many other ECM proteins, tenascins promote only weak cell adhesion and do not activate cell spreading. They have been classified as anti-adhesive, adhesion-modulating or even repellent ECM proteins. Tenascin-C and tenascin-R deficient mice show abnormalities in the nervous system and tenascin-C deficient mice, in addition, have defects in several regenerative processes. Mice lacking tenascin-X display hyperelastic skin much like Ehlers Danlos patients with mutations in their tenascin-X gene. Since tenascin-C is highly overexpressed in tumor stroma antibodies against tenascin-C have been used in tumor diagnosis and therapy. Since tenascins are known to influence cell shape, migration and growth they represent good candidate molecules for inclusion in artificial bioengineered tissue implants.

Introduction

Cell–cell and cell–extracellular matrix (ECM) interactions are important in regulating normal development of multicellular organisms. Cells in tissues constantly sense their environment by cell surface receptors that interact with ligands on neighboring cells and with molecules of the ECM. These interactions control cellular behavior and morphology and thus influence cell growth and differentiation. It is, therefore, important to analyze the structure of the ECM and to characterize the specific components present in the different ECMs. Tenascins are a family of glycoproteins present in many ECMs throughout our bodies (for recent reviews see Chiquet-Ehrismann & Chiquet, 2003; Jones & Jones, 2000). Vertebrate genomes harbor four tenascin genes whereas this gene family has not been found outside the phylum Chordata and is not present in C. elegans or Drosophila. The four tenascins have been termed tenascin-C (myotendinous antigen, GMEM, cytotactin), tenascin-R (restrictin, janusin), tenascin-X (gene X) and teanscin-W (tenascin-N).

Section snippets

Structure

All tenascins are built from a common set of structural motifs represented in Fig. 1. The protein modules making up tenascins include heptad repeats, EGF-like repeats, fibronectin type III domains, and a C-terminal globular domain shared with fibrinogens. These protein modules are lined up like beads on a string and give rise to long and extended molecules. At the N-terminus each tenascin has an oligomerization domain which in the case of tenascin-C and -W leads to the formation of hexamers

Synthesis

Tenascins are synthesized primarily by cells in connective tissues (cf. this issue). However, each of the tenascins has a typical expression pattern that differs from all other tenascins. Thus, tenascin-R is exclusively present in the central nervous system. Tenascin-C is also present in the central nervous system and in addition, is a prominent constitutent of perpipheral nerves (for review see Joester & Faissner, 2001). Furthermore, tenascin-C is highly expressed during embryogenesis and is

Biological function

Many ECM proteins are effective in promoting cell attachment and cell spreading. Tenascins, to the contrary, promote only weak cell attachment and cell spreading is limited. This is shown for tenascin-C and -W in Fig. 2. Tenascin-C was found to inhibit cell adhesion of many cell types to fibronectin and can thus be classified as an adhesion-modulating protein (Orend & Chiquet-Ehrismann, 2000). The mechanism of action of tenascin-C is summarized in the accompanying article on tenascin-C

Possible medical applications

In the case of tenascin-C, antibodies have been used for diagnosis and therapy of many different cancers (for a recent review see Chiquet-Ehrismann & Chiquet, 2003)). It was found that tenascin-C expression correlated with angiogenesis and local infiltration of normal tissue by tumor cells of various types of carcinomas.

Another promising medical application for ECM proteins will be their use to modify tissue implants, e.g. to improve and accelerate integration of joint replacements into the

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