The International Journal of Biochemistry & Cell Biology
Molecules in focusTenascins
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
References (20)
- et al.
The structure and function of tenascins in the nervous system
Matrix Biology
(2001) - et al.
Adhesion modulation by antiadhesive molecules of the extracellular matrix
Experimental and Cell Research
(2000) - et al.
The F3/11 cell adhesion molecule mediates the repulsion of neurons by the extracellular matrix glycoprotein J1-160/180
Neuron
(1993) - et al.
Biomimetic materials for tissue engineering
Biomaterials
(2003) - et al.
Tenascin-R induces actin-rich microprocesses and branches along neurite shafts
Molecular and Cellular Neuroscience
(2002) - et al.
Tenascin-R as a repellent guidance molecule for developing optic axons in zebrafish
Journal of Neuroscience
(2003) - et al.
Tenascins: Regulation and putative functions during pathological stress
Journal of Pathology
(2003) - et al.
Tenascin-C expression by fibroblasts is elevated in stressed collagen gels
Journal of Cell Biology
(1994) - et al.
Abnormal reinnervation of skeletal muscle in a tenascin-C-deficient mouse
Journal of Neuroscience Research
(2002) - et al.
Cell adhesion to tenascin-X mapping of cell adhesion sites and identification of integrin receptors
European Journal of Biochemistry
(1999)
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2019, Journal of ProteomicsCitation Excerpt :The Khib sites in tenascin were the most significant and most upregulated in the comparison between PP and PN (ratio = 3.082, p = .0307). Tenascin-C is a member of the tenascin gene family [27,28], which has been shown to be upregulated under pathological conditions caused by inflammation, infection, tumorigenesis, and other mechanisms [29]. Studies have found increased tenascin-C levels in the circulating blood of patients with psoriasis [30].
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2018, Mechanisms of DevelopmentCitation Excerpt :Among tenascins we detected the expression of tenascin-C (Tnc) only in interstitial/stromal cells. Tenascin-C interacts with ECM components such as fibronectin leading to the upregulation of matrix metalloproteinases (Chiquet-Ehrismann, 2004). It is important for tissue remodeling and cell adhesion.