Fibronectins, Their Fibrillogenesis, and In Vivo Functions

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Cold Spring Harbor perspectives in biology (Impact Factor: 8.68). 05/2011; 3(7). DOI: 10.1101/cshperspect.a005041
Source: PubMed


Fibronectin (FN) is a multidomain protein with the ability to bind simultaneously to cell surface receptors, collagen, proteoglycans, and other FN molecules. Many of these domains and interactions are also involved in the assembly of FN dimers into a multimeric fibrillar matrix. When, where, and how FN binds to its various partners must be controlled and coordinated during fibrillogenesis. Steps in the process of FN fibrillogenesis including FN self-association, receptor activities, and intracellular pathways have been under intense investigation for years. In this review, the domain organization of FN including the extra domains and variable region that are controlled by alternative splicing are described. We discuss how FN-FN and cell-FN interactions play essential roles in the initiation and progression of matrix assembly using complementary results from cell culture and embryonic model systems that have enhanced our understanding of this process.

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    • "Chemical and mechanical signals emanating from the fibronectin matrix are transduced through the integrin family of adhesion receptors. Matrix-based signals integrate with those from signaling pathways initiated through growth factors, cytokines and intercellular adhesion receptors (Schwarzbauer and DeSimone, 2011). It is through these matrix-based signaling networks that fibronectin exerts its influence over nearly all aspects of endothelial cell biology (Astrof and Hynes, 2009; Malinin et al., 2012). "
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    • "Modification with fibronectin can be used to study effects of cell attachment. Fibronectin (Fn) is an extracellular glycoprotein that binds both cell integrins and other ECM molecules, and plays a major role in cell adhesion, growth and differentiation [42]. This glycoprotein is also important for neural development by promoting cell survival, migration, neurite outgrowth and synapse formation [43]. "
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    • "Normally it is integrins (cell membrane protein) that connect cells, including prostatic epithelial cells, to the ECM by binding to fibronectin already present in the matrix 47. This interaction is required for proper assembly of fibronectin in the matrix, something that is very important for ECM organization and stability 48, 49. Cancer typically involves an epithelial to mesenchymal transition (EMT), whereby malignant cells can now break loose of their defined position within the microenvironment. "
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