"Beads-on-a-string" filaments: structure, functions and associated pathologies

Elastic fibers are extracellular amorphous aggregates which provide elastic ity to numerous organs, and which can vary in size and arrangement dependin g on biomechanical requirements. All elastic fibers are characterized by a more or less important amorphous core of cross-linked elastin surrounded by a peripheral mantle of microfibrils, With a diameter of 10-12 nm and avera ge axial periodicity of 55 nn, microfibrils are also found in non-elastic t issues. In elastic tissues, they are thought to act as an organizing scaffo ld upon which tropoelastin is subsequently deposited. In nonelastic tissues , microfibrils may act as an anchoring structure between epithelia and thei r surrounding matrix or between adjacent epithelia. In addition to ultrastr uctural descriptive studies, increasing knowledge is available concerning m icrofibril composition. Based on biochemical and immunochemichal data, seve ral microfibrillar proteins have been identified, At least three groups of proteins are believed to contribute to microfibrillar architecture: fibrill in, MAGP (microfibril associated glycoProtein) and LTBP (latent transformin g growth factor-p binding protein). Fibrillins 1 and 2 are known to be the major components of microfibrils; MAGP-1 and LTBP-1 also appear to be micro fibril components, whereas MAGP-2 and LTBP-2 have been found to be either c o-localized or poorly associated with microfibrils. The importance of the 3 50 kDa proteins, fibrillins, has been underlined by mutations in the genes coding for fibrillin-1 and fibrillin-2 which have been correlated with two major connective tissue diseases, Marfan syndrome (MFS) and Beals syndrome also named Congenital Contractural ARachnodactyly (CCA). Consequently, many fibrillar functions have emerged. For example, besides their ability to gu ide elastogenesis, fibrillin microfibrils appear to link elastic fibers bot h to each other and to other extracellular matrix components. Anchoring the cells to the matrix, they can also influence cellular behaviour. Furthermo re, they are able, like collagen VI microfibrils, to modulate the platelet response to blood vessel injury.