Fibronectin is a glucoprotein and plays a major role in the cohesion of body cells or in blood clotting. In the organism, it performs many different functions related to its ability to form adhesive forces. Structural defects in the formation of fibronectin can lead to severe connective tissue weaknesses.
What is fibronectin?
Fibronectin represents a glucoprotein with a molecular weight of 440 kDa (kilodaltons). It serves to form adhesion forces between cells, between body cells and various substrates, between body cells and the intercellular matrix, and between platelets during blood clotting. Therefore, it supports wound healing, embryogenesis, hemostasis, cell adhesion during cell migration or antigen binding to phagocytes. Primary fibronectin contains 2355 amino acids and forms 15 isoforms. It is found in the extracellular area as well as inside somatic cells. Outside the cells it represents an insoluble protein. Inside the cell plasma it is a soluble protein. All forms of fibronectin are encoded by the same FN1 gene. Soluble fibronectin contains two isomeric protein chains linked by a disulfide bridge. In insoluble fibronectin, these molecules are connected to each other again by disulfide bridges to form a fibril-like structure.
Anatomy and structure
In basic structure, fibronectin represents a heterodimer of two rod-like protein chains. These are connected by a disulfide bridge. The isomeric protein chains are expressed from the same gene, the FN1 gene. The different base sequence results from alternative splicing of this gene. Each gene contains exons and introns. Exons are segments that are translated into protein structure. Introns, on the other hand, are inactive gene segments. In alternative splicing, the sequence of base pairs remains the same, but exons and introns are found at different gene segments. In the translation of genetic information, the readable exons are spliced together and the introns are excised. This alternative translation of the same genetic information allows the formation of multiple isomeric protein chains from the same gene. The fibronectin formed from two isomeric protein chains is soluble, is formed in the liver and enters the blood plasma. There it is responsible for the coagulation of blood in the context of wound healing and tissue regeneration. Insoluble fibronectin is produced in macrophages, endothelial cells or fibroblasts. It contains the same basic structure. Here, however, the individual fibronectin molecules are again linked together by disulfide bridges to form fibrillar protein structures that hold the cells together. The ability to form adhesive forces is due to the frequently occurring amino acid sequence arginine-glycine-aspartate. This results in the adhesion of fibronectin to so-called integrins (adhesion receptors on the surface of the cells). The protein chains of fibronectin are composed of many domains containing 40 to 90 amino acids. Based on the homology of the domains, fibronectin polypeptide chains are classified into three structural types, I, II, and III.
Function and roles
Fibronectin generally serves to hold certain structural units together. These include cells, the extracellular matrix, certain substrates, and platelets. In the past, fibronectin was therefore also referred to as cell glue. It ensures that the cells in the tissues stay together and do not drift apart. It also plays a major role in cell migration. Even the docking of macrophages to antigens is mediated by fibronectin. Furthermore, fibronectin also controls many processes of embryogenesis and cell differentiation. However, in malignant tumors, fibronectin is often decreased. This enables the tumor to grow into the tissue and form metastases by shedding tumor cells. In blood plasma, soluble fibronectin enables the formation of blood clots to close bleeding wounds. In this process, the individual blood platelets are stuck together by fibrin formation. As an opsonin, fibronectin binds to the surface of macrophages as receptors. With the help of these receptors, the macrophages can bind and incorporate certain pathogenic particles.In the extracellular space, insoluble fibronectin is responsible for the formation of a matrix that fixes the cells.
Diseases
Deficiency or structural abnormalities of fibronectin often have serious health consequences. For example, as a result of cancer growth within the tumor, fibronectin concentration decreases. The cell association within the tumor becomes looser and the cells migrate apart. This leads to the frequent metastases caused by tumor cells splitting off and migrating through the lymphatic system or blood plasma to other parts of the body. In addition, due to the lack of fibronectin, the cancer cells can also grow more quickly into the neighboring tissue and thus displace it. Furthermore, there are hereditary diseases that lead to a defect of the connective tissue. One example is Ehlers-Danlos syndrome. Ehlers-Danlos syndrome is not a single disease, but represents a complex of connective tissue defects. Type X is caused by absent or defective fibronectin. It is a mutation in the FN1 gene. This results in a drastic weakness of the connective tissue. The disease is inherited in an autosomal recessive manner. It is manifested by very flabby skin and hypermobility of the joints. Despite great differences in the cause of connective tissue weakness, the symptoms of individual diseases of this complex are similar. According to the Danish dermatologist Edvard Ehlers and the French dermatologist Henri-Alexandre Danlos, the cardinal symptoms of Ehlers-Danlos syndrome are severe overstretching and tearing of the skin. Finally, a certain mutation in the FN1 gene can also lead to glomerulopathy (diseases of the renal corpuscles). This is a serious kidney disease that often requires dialysis treatment.
