Figure 3.
Major steps in fibronectin (FN) matrix assembly. Integrin-induced conversion of compact FN to extended fibrils is shown in four steps. (a) A compact FN dimer binds to integrins ( gray). FN subunits of a single dimer are shown in two shades of orange. (b) Intracellular proteins ( pink, yellow, blue) are recruited to integrin cytoplasmic domains and connected to the actin cytoskeleton ( green). Cytoskeletal connections increase cell contractility (arrows), which induces conformational changes in FN. (c) Integrin clustering and exposed FN-binding sites promote FN-FN interactions and further changes in FN conformation. (d ) Finally, these events trigger formation of stable insoluble fibrillar matrix. The inset (red box) shows interactions between single subunits of FN dimers. N indicates the N terminus of an FN subunit. Fibrils form through (i) end-to-end association of FN dimers, mediated by the N -terminal assembly domain, followed by (ii) lateral associations between fibrils that are likely to involve the other FN-binding sites in III1–2, III4–5, and III12–14. Gray X’s represent interactions between fibrils.