Microfibrils and Fibrillin

Abstract

Microfibrils are supramolecular structures ubiquitously found in the extracellular matrix of elastic and nonelastic tissues. The three members of the cysteine-rich fibrillin family constitute the core of microfibrils. Mutations in fibrillin-1 and -2 lead to a number of heritable connective tissue disorders termed fibrillinopathies. Clinical symptoms affect blood vessels, bone, the eye, and other organ systems and highlight the importance of fibrillins in development and homeostasis of tissues and organs. Microfibrils have functional significance (1) in conferring mechanical stability and limited elasticity to tissues; (2) in the biogenesis and maintenance of the elastic fiber system; and (3) in the modulation of the activity of growth factors, including transforming growth factor-β and several bone morphogenetic proteins. In this chapter, we provide an overview of the structure, assembly, and functions of fibrillins and microfibrils and also the pathobiology associated with genetic aberrations in the microfibril system. Lessons learned from mouse models will be discussed as well as the emerging role of microfibrils and fibrillins in the regulation of growth factor bioavailability. Due to the large number of articles in the field, we repeatedly cite excellent review articles to which interested readers are referred to for more details.