Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions.
This study establishes that the physical state of the extracellular matrix can regulate integrin-mediated cytoskeletal assembly and tyrosine phosphorylation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, alpha(5)beta(1) integrin associates mainly with fibronectin fibrils and forms adhesions structurally distinct from focal contacts, independent of actomyosin-mediated cell contractility. These "fibrillar adhesions" are enriched in tensin, but contain low levels of the typical focal contact components paxillin, vinculin, and tyrosine-phosphorylated proteins. However, when the fibronectin is covalently linked to the substrate, alpha(5)beta(1) integrin forms highly tyrosine-phosphorylated, "classical" focal contacts containing high levels of paxillin and vinculin. These experiments indicate that the physical state of the matrix, not just its molecular composition, is a critical factor in defining cytoskeletal organization and phosphorylation at adhesion sites. We propose that molecular organization of adhesion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate cytoplasmic anchor proteins (e.g., fibronectin-alpha(5)beta(1) integrin-tensin complexes), and 2) physical properties (e.g., rigidity) of the extracellular matrix regulate local tension at adhesion sites and activate local tyrosine phosphorylation, recruiting a variety of plaque molecules to these sites. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts.
Katz
B Z
BZ
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Craniofacial and Dental Research, National Institutes of Health, Bethesda, MD, USA.
Zamir
E
E
Bershadsky
A
A
Kam
Z
Z
Yamada
K M
KM
Geiger
B
B
D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry* / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D019000:Phosphotyrosine / Q000378:metabolism
D005353:Fibronectins; D019000:Phosphotyrosine