CELLULAR FIBRONECTIN’S ROLE IN EXTRACELLULAR MATRIX FORMATION
All highly evolved metazoan organisms have unique to there own species, a highly complex, dynamic, specific extracellular matrixes that surround all of their cells, organs, neural complexes, vascular systems, etc. Within each species, the organization of the extracellular matrices are further unique to each differentiated cell group, each organ, vascular complexes, neuronal systems, skin, oral cavity, digestive systems, etc.
Within the past decade, research has shown that the extracellular matrix (ECM) is a dynamic active zone that functions to interact with its specific cellular phenotype. The ECM interacts directly with cell surface receptors, (integrins) to initiate signal transduction pathways to modulate differentiation, and to control the activity of a wide range of growth factors, cytokins, and survival factors. The classical view of the ECM as a physical support barrier, has been extended by its additional role as an instructional entity of all the cells and organs residing on or within it. (Streuli, 1999)
Cellular Fibronectin (cFN) plays a profound role in the initiation of ECM deposition as well as its total organization and composition. The polymerization of cFN matrix is also a critical regulator of ECM stability. Further, cFN polymerization acts as a switch that controls cell matrix adhesive sites providing cells with a means of precisely controlling cell extracellular matrix signaling events that regulate many aspects of cell behavior including cell proliferation, migration, and differentiation. (Sottile and Hockings, 2002)
Transforming growth factor-beta (TGF beta) is a highly essential component of the ECM. In a complex manner, cFN regulates TGF beta. Latent transforming growth factor-beta- binding proteins (LTBPs) are ECM glycoproteins that play a major role in the storage of latent TGF beta in the ECM and regulate its availability.
Immunolocalization studies show that a cFN scaffold is critical for the incorporation of LTBP1 and TGF beta into the ECM of osteoblasts and fibroblasts. Not only was cFN essential for the initial incorporation of LTBP1 into the ECM, but the continued presence of cFN was required for the continued assembly of LTBP1. Studies by (Dallas, et al 2005) highlight a nonredundant role for cFN in LTBP1 assembly into the ECM and suggest a novel role for cFN in regulation of TGF beta via LTBP1 interactions.
Collagens are a diverse family of proteins, the most prevalent molecules in higher metazoan organisms. They are components in almost all tissues and the most predominant collagens are I and III. (Eyre 1980). (Velling et al 2002) had studied the role of collagen receptors, integrins alpha (11) beta (1) and alpha (2) beta (1), and fibronectin in collagen polymerization using fibronectin-deficient mouse embryonic fibroblasts cell lines. In contrast to the earlier belief that collagen polymerization occurs via self-assembly of collagen molecules, their research shows that a performed cFN matrix is essential for collagen network formation and that collagen-binding integrins strongly enhance this process. Therefore, collagen deposition is regulated by the cells, both indirectly through integrin alpha (5) beta (1) dependent polymerization of cFN and directly through collagen binding integrins.
Streuli, Charles. Extracellular matrix remoddling and cellular differentiation. Current Opinion in Cell Biology 1999, 11: 634-640
Sottile J, and Hocking DC. Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions. Mol Biol Cell. 2002 Oct; 13 (10) : 3546-59.
Dallas SL, et al. Fibronectin regulates transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. J Biol Chem. 2005 May 13: 280 (19) : 18871-80. Epub 2005 Jan 27.
Eyre DR. Collagen: molecular diversity in the body?s protein scaffold. Science. 1980 Mar 21: 207 (4437) : 1315-22.
Velling T, et al. Polymerization of type I and III collagens is dependent on fibronectin and enhanced by integrins alpha 11 beta 1 and alpha 2 beta 1. J Biol Chem. 2002 Oct 4; 277 (40) : 37377-81. Epub 2002 Jul 26.