Evolutionary Insights into Fibrillin Structure and Function in the Extracellular Matrix

The 10–12 nm diameter microfibrils of the extracellular matrix are vital components of dynamic tissues, playing a major role in providing the tissues of metazoan species with their biomechanical properties. They also have functional roles in the development of elastic fibres, as a scaffold for the deposition of tropoelastin, and in the regulation of growth factors. Fibrillins are large, ~350 kDa glycoproteins that assemble to form the microfibrils. Throughout evolution, the fibrillins show a remarkably conserved domain organisation, dominated by calcium-binding epidermal growth factor domains interspersed with transforming growth factor-β-binding protein-like domains. Mutations in the fibrillin genes cause a range of human diseases including Marfan syndrome, Beals syndrome, stiff skin syndrome and the acromelic dysplasias, which affect the skin, skeleton, ocular and cardiovascular systems. In recent years, studies using molecular, cellular and animal models have yielded new information on the processes of microfibril assembly and organisation and how their regulation of growth factors is involved in disease pathogenesis. Recent advances in bioinformatics and the availability of whole genome sequences are now providing new insights into the functions of different regions of the fibrillin polypeptides, helping us to understand how fibrillin structure and function has evolved as the extracellular matrix has increased in complexity.