Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1363-1370
© 1998 American Heart Association, Inc.
Brief Reviews |
Fibronectin
Structure, Assembly, and Cardiovascular Implications
From the Department of Medicine, University of Wisconsin–Madison.
Correspondence to Deane F. Mosher, Department of Medicine, University of Wisconsin–Madison, 1300 University Ave, Madison, WI 53706. E-mail dfmosher@facstaff.wisc.edu
Key Words: fibronectin • integrins • cytoskeleton • lysophosphatidic acid
In the past 2 decades, it has been appreciated that the functions of the extracellular matrix (ECM) are not entirely structural. ECM components interact with specific adhesion receptors on cell surfaces and regulate various cellular functions, including differentiation, proliferation, migration, and apoptosis. Fibronectin (FN) is a paradigm adhesive protein, nonreactive with adhesion receptors in its soluble state but highly adhesive when insoluble. Polymerization of FN into the ECM must be tightly regulated to ensure that the adhesive information in the ECM is appropriate.
FN exists in a soluble protomeric form in micromolar concentration in
blood plasma and in an insoluble multimeric form in the
ECM.1 2 Unlike fibrillar or basement membrane
collagens, laminins, actin, and tubulin, circulating FN does not
self-polymerize in physiologically relevant
solutions. Furthermore, there is little passive accumulation of FN in
preexisting ECM. Rather, assembly of FN takes place at specialized
areas on the cell surface.3 FN is especially
abundant in the ECM of embryonic and regenerating or injured tissues,
although it can be found in most ECMs, including basement membranes. FN
interacts with cells through integrins, heterodimeric transmembrane
receptors linking the ECM to the intracellular cytoskeleton and
signaling pathways. The aim of this review is to describe the
mechanisms and consequences of FN deposition and give a brief overview
of the significance of FN for selected areas of
cardiovascular research. In the first section we
describe important features of the FN molecule that account for its
multiple functions. Next, we focus on the assembly process, ie, the
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