Assembly of fibrillin microfibrils governs extracellular deposition of latent TGFβ

• DOI: 10.1242/jcs.073437
• Publication Date: 2010-08-11T04:24:54Z
• Authors: Teresa Massam-Wu; Maybo Chiu; Rawshan Choudhury; Shazia S. Chaudhry; Andrew K. Baldwin; Amanda McGovern; Clair Baldock; C. Adrian Shuttle...; Cay M. Kielty
• Keywords: Fibrillin; Microfibril

Control of the bioavailability growth factor TGFbeta is essential for tissue formation and homeostasis, yet precisely how latent incorporated into extracellular matrix unknown. Here, we show that deposition a large complex (LLC), which contains TGFbeta-binding protein 1 (LTBP-1), directly dependent on pericellular assembly fibrillin microfibrils, interact with fibronectin during higher-order fibrillogenesis. LTBP-1 formed arrays colocalized whereas knockdown inhibited fibrillar and/or LLC deposition. Blocking alpha5beta1 integrin or supplementing cultures heparin, both microfibril assembly, disrupted enhanced Smad2 phosphorylation. Full-length bound only weakly to N-terminal pro-fibrillin-1, but this association was strongly by heparin. The microfibril-associated glycoprotein MAGP-1 (MFAP-2) binding fibrillin-1 stimulated By contrast, fibulin-4, interacted full-length LTBP-1, did not induce Thus, governed interactions between heparan sulfate, molecules. In way, microfibrils control bioavailability.