New insights into the structure, assembly and biological roles of 10–12 nm connective tissue microfibrils from fibrillin-1 studies

Jensen, Sacha A., and Handford, Penny A. (2016) New insights into the structure, assembly and biological roles of 10–12 nm connective tissue microfibrils from fibrillin-1 studies. Biochemical Journal, 473 (7). pp. 827-838.

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Abstract

The 10–12 nm diameter microfibrils of the extracellular matrix (ECM) impart both structural and regulatory properties to load-bearing connective tissues. The main protein component is the calcium-dependent glycoprotein fibrillin, which assembles into microfibrils at the cell surface in a highly regulated process involving specific proteolysis, multimerization and glycosaminoglycan interactions. In higher metazoans, microfibrils act as a framework for elastin deposition and modification, resulting in the formation of elastic fibres, but they can also occur in elastin-free tissues where they perform structural roles. Fibrillin microfibrils are further engaged in a number of cell matrix interactions such as with integrins, bone morphogenetic proteins (BMPs) and the large latent complex of transforming growth factor-β (TGFβ). Fibrillin-1 (FBN1) mutations are associated with a range of heritable connective disorders, including Marfan syndrome (MFS) and the acromelic dysplasias, suggesting that the roles of 10–12 nm diameter microfibrils are pleiotropic. In recent years the use of molecular, cellular and whole-organism studies has revealed that the microfibril is not just a structural component of the ECM, but through its network of cell and matrix interactions it can exert profound regulatory effects on cell function. In this review we assess what is known about the molecular properties of fibrillin that enable it to assemble into the 10–12 nm diameter microfibril and perform such diverse roles

Item ID: 60809
Item Type: Article (Research - C1)
ISSN: 1470-8728
Funders: Arthritis Research UK (AR), Medical Research Council, UK (MRC)
Projects and Grants: AR grant 20785, MRC grant MR/M009831/1
Date Deposited: 05 Nov 2019 23:51
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060112 Structural Biology (incl Macromolecular Modelling) @ 50%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060106 Cellular Interactions (incl Adhesion, Matrix, Cell Wall) @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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