TGF-β₁Binding Protein-Like Modules of Fibrillin-1 and -2 Mediate Integrin-Dependent Cell Adhesion

Abstract

Human fibrillin, a major component of the extracellular matrix, exists as two highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells were used in microassays of cell attachment and cell spreading on fibrillin fusion-protein substrata. Dose-dependent experiments and competitive inhibition by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD-dependent cell adhesion. These results provide evidence for a cell adhesion function of fibrillin-2. Inhibition with anti-integrin antibodies showed that alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v) and beta1 are involved in adhesion to D12-2. Binding of different receptors may elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and fibrillin-2 have distinct roles.

αVβ6 Is a Novel Receptor for Human Fibrillin-1

“…Earlier cell adhesion assays with function-blocking antibodies, performed on purified microfibrils and recombinant fibrillin-1 fragments, suggested that ␣5␤1 integrin functions as a fibrillin-1 receptor in certain cell lines (7,26). However, several attempts to demonstrate this interaction in a cell-free system have been unsuccessful (4,8).…”

Fibrillin-1 expression in normal and fibrotic rat liver and in cultured hepatic fibroblastic cells: modulation by mechanical stress and role in cell adhesion

“…12,13 Thus, fibrillin may act as a classical adhesion protein. 12,13,41,42 However, our Immunofluorescence staining was quantified at the microscopic level and expressed as a percentage of stained areas per field. Significant differences were observed in fibroblastic cells cultured for 5 days compared with fibroblastic cells cultured for 2 days (Po0.02 for both rat and human fibroblasts), and in restrained collagen lattices compared with unrestrained collagen lattices (Po0.03 at 2 days for both rat and human fibroblasts; Po0.01 at 5 days for both rat and human fibroblasts).…”

Medical Management of Marfan Syndrome

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