The Multiple Functions of Fibrillin-1 Microfibrils in Organismal Physiology

Abstract

Fibrillin-1 is the major structural component of the 10 nm-diameter microfibrils that confer key physical and mechanical properties to virtually every tissue, alone and together with elastin in the elastic fibers. Mutations in fibrillin-1 cause pleiotropic manifestations in Marfan syndrome (MFS), including dissecting thoracic aortic aneurysms, myocardial dysfunction, progressive bone loss, disproportionate skeletal growth, and the dislocation of the crystalline lens. The characterization of these MFS manifestations in mice, that replicate the human phenotype, have revealed that the underlying mechanisms are distinct and organ-specific. This brief review summarizes relevant findings supporting this conclusion.

Keywords: Marfan syndrome; bone lengthening; dilated cardiomyopathy; fibrillin-1; lens dislocation; osteopenia; thoracic aortic aneurysm.

Figure 1

Panel (A), overall scheme of the main steps in the biosynthesis of 10 nm microfibrils and elastic fibers with indicated interactions discussed in the text. Panel (B), a summary of the mechanisms underlying selected clinical manifestations characterized in MFS mice.