Fibronectin Is An Important Glycoprotein Involved In Cell Adhesion Migration

Fibronectin is a major glycoprotein of the extracellular matrix, also found in a soluble form in plasma. It consists of two identical subunits, each of about 230 kDa, joined by two disulfide bridges near their carboxyl terminals. The gene encoding fibronectin is very large, containing some 50 exons; the RNA produced by its transcription is subject to considerable alternative splicing, and as many as 20 different mRNAs have been detected in various tissues. Fibronectin contains three types of repeating motifs (I, II, and III), which are organized into functional domains (at least seven); functions of these domains include binding heparin (see below) and fibrin, collagen, DNA, and cell surfaces (Figure 48-3). The amino acid sequence of the fi-bronectin receptor of fibroblasts has been derived, and the protein is a member of the transmembrane integrin class of proteins (Chapter 51). The integrins are het-erodimers, containing various types of a and P polypeptide chains. Fibronectin contains an Arg-Gly-Asp (RGD) sequence that binds to the receptor. The RGD sequence is shared by a number of other proteins present in the ECM that bind to integrins present in cell surfaces. Synthetic peptides containing the RGD sequence inhibit the binding of fibronectin to cell surfaces. Figure 48-4 illustrates the interaction of collagen, fibronectin, and laminin, all major proteins of the

Figure 48-2. Probable sequence of events in the causation of the major signs exhibited by patients with Marfan syndrome (MIM 154700).

ECM, with a typical cell (eg, fibroblast) present in the matrix.

The fibronectin receptor interacts indirectly with actin microfilaments (Chapter 49) present in the cy-tosol (Figure 48-5). A number of proteins, collectively known as attachment proteins, are involved; these include talin, vinculin, an actin-filament capping protein, and a-actinin. Talin interacts with the receptor and vinculin, whereas the latter two interact with actin. The interaction of fibronectin with its receptor provides one route whereby the exterior of the cell can communicate with the interior and thus affect cell behavior. Via the interaction with its cell receptor, fibronectin plays an important role in the adhesion of cells to the ECM. It is also involved in cell migration by providing a binding site for cells and thus helping them to steer their way through the ECM. The amount of fibronectin around many transformed cells is sharply reduced, partly explaining their faulty interaction with the ECM.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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