Fibronectin polymerization regulates the composition and stability of extracellular matrix fibrils and cell-matrix adhesions.
Remodeling of extracellular matrices occurs during development, wound healing, and in a variety of pathological processes including atherosclerosis, ischemic injury, and angiogenesis. Thus, identifying factors that control the balance between matrix deposition and degradation during tissue remodeling is essential for understanding mechanisms that regulate a variety of normal and pathological processes. Using fibronectin-null cells, we found that fibronectin polymerization into the extracellular matrix is required for the deposition of collagen-I and thrombospondin-1 and that the maintenance of extracellular matrix fibronectin fibrils requires the continual polymerization of a fibronectin matrix. Further, integrin ligation alone is not sufficient to maintain extracellular matrix fibronectin in the absence of fibronectin deposition. Our data also demonstrate that the retention of thrombospondin-1 and collagen I into fibrillar structures within the extracellular matrix depends on an intact fibronectin matrix. An intact fibronectin matrix is also critical for maintaining the composition of cell-matrix adhesion sites; in the absence of fibronectin and fibronectin polymerization, neither alpha5beta1 integrin nor tensin localize to fibrillar cell-matrix adhesion sites. These data indicate that fibronectin polymerization is a critical regulator of extracellular matrix organization and stability. The ability of fibronectin polymerization to act as a switch that controls the organization and composition of the extracellular matrix and cell-matrix adhesion sites provides 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
Jane
J
Department of Medicine, Center for Cardiovascular Research, Rochester, New York 14642, USA. jane_sottile@urmc.rochester.edu
Hocking
Denise C
DC
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D021982:Cell-Matrix Junctions / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D047630:Depsipeptides; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D011108:Polymers / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019700:Thrombospondin 1 / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D024042:Collagen Type I; D047630:Depsipeptides; D005353:Fibronectins; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011108:Polymers; D011480:Protease Inhibitors; D019700:Thrombospondin 1; C057531:jasplakinolide; D020928:Mitogen-Activated Protein Kinases