Tenascin-X is a large protein found in the spaces between cells, an area known as the extracellular matrix. It is produced by the TNXB gene and plays a part in organizing and maintaining the structure of connective tissues that support muscles, joints, organs, and skin throughout the body. The discovery of Tenascin-X was incidental, identified during research into steroid production disorders rather than connective tissue studies. Its presence is widespread, contributing to the structural integrity of various tissues and organs.
Understanding Tenascin X Structure and Distribution
Tenascin-X is the largest member of the tenascin family of glycoproteins, which are complex proteins bonded to carbohydrates. The protein is assembled from multiple distinct domains, including sections that resemble parts of other proteins like fibronectin and fibrinogen. This modular construction allows it to assemble into larger structures and interact with many other components of the extracellular matrix.
These complex assemblies are found extensively throughout the body’s loose connective tissues. Tenascin-X is specifically located in the connective tissue of skin, tendons, ligaments, muscles, and blood vessels. Within these tissues, it is found at the surface of or between collagen fibrils, the fundamental building blocks of connective tissue.
Essential Functions of Tenascin X
The primary role of Tenascin-X is to organize the extracellular matrix, ensuring the stability and integrity of connective tissues. It accomplishes this by physically interacting with several types of collagen. These interactions help to regulate the spacing and organization of collagen fibrils, which is necessary for the proper mechanical strength of tissues like skin and tendons.
Beyond its architectural duties, Tenascin-X also influences the properties of elastic fibers, which give tissues their ability to stretch and recoil. The protein helps to regulate the structure and stability of these fibers, contributing to the overall flexibility of connective tissues. It also interacts with decorin, a smaller protein that has a role in the formation of collagen fibrils, and can modulate cell adhesion.
Consequences of Tenascin X Deficiency
A lack of functional Tenascin-X protein, caused by mutations in both copies of the TNXB gene, leads to a rare condition known as classical-like Ehlers-Danlos syndrome (clEDS). A complete absence of the protein severely disrupts the organization of both collagen and elastic fibers, which weakens these tissues throughout the body.
Individuals with clEDS typically exhibit skin that is highly elastic and fragile, along with significant joint hypermobility, meaning their joints have an unusually large range of movement. Unlike some other forms of Ehlers-Danlos syndrome, this type does not usually involve severe atrophic scarring. People with mutations affecting only one copy of the TNXB gene may produce a reduced amount of Tenascin-X. This can lead to conditions like the hypermobile type of Ehlers-Danlos syndrome or benign joint hypermobility syndrome, characterized by joint instability and chronic pain.
Current Research and Wider Significance
Current research continues to explore functions of Tenascin-X beyond its established architectural role, including its involvement in cell signaling pathways. For example, studies have shown that Tenascin-X can regulate the availability of Transforming Growth Factor-β (TGF-β), a molecule involved in tissue fibrosis. This suggests Tenascin-X may have a part in modulating tissue repair and response to injury.
The protein’s anti-adhesive properties, which can prevent cells from sticking to the matrix, are being explored to understand how it might affect cell migration and tissue development. There is also emerging evidence that links Tenascin-X to conditions beyond clEDS, with research exploring its potential involvement in inflammatory processes and cardiovascular diseases. Understanding these broader functions could open new avenues for diagnostics and treatments for a wider range of disorders.