New insights into elastic fiber assembly

Abstract

Elastic fibers provide recoil to tissues that undergo repeated stretch, such as the large arteries and lung. These large extracellular matrix (ECM) structures contain numerous components, and our understanding of elastic fiber assembly is changing as we learn more about the various molecules associated with the assembly process. The main components of elastic fibers are elastin and microfibrils. Elastin makes up the bulk of the mature fiber and is encoded by a single gene. Microfibrils consist mainly of fibrillin, but also contain or associate with proteins such as microfibril associated glycoproteins (MAGPs), fibulins, and EMILIN-1. Microfibrils were thought to facilitate alignment of elastin monomers prior to cross-linking by lysyl oxidase (LOX). We now know that their role, as well as the overall assembly process, is more complex. Elastic fiber formation involves elaborate spatial and temporal regulation of all of the involved proteins and is difficult to recapitulate in adult tissues. This report summarizes the known interactions between elastin and the microfibrillar proteins and their role in elastic fiber assembly based on in vitro studies and evidence from knockout mice. We also propose a model of elastic fiber assembly based on the current data that incorporates interactions between elastin, LOXs, fibulins and the microfibril, as well as the pivotal role played by cells in structuring the final functional fiber. Birth Defects Research (Part C) 81:229-240,

Co-expression of FBN1 with mesenchyme-specific genes in mouse cell lines: implications for phenotypic variability in Marfan syndrome

“…36 No disease has been associated with BGN mutation in humans but Bgn-deficient mice have a skeletal phenotype. 37 Lysyl oxidase (Lox gene) may be important in overall assembly of elastic microfibrils (reviewed in Wagenseil and Mecham 38 ) and may be involved in preparing tumour cells for metastasis. 39 The human homologue of another of the cluster genes, SERPINH1, was recently implicated in a recessive form of osteogenesis imperfecta, a bone disease.…”

NMR and Bioinformatics Discovery of Exosites That Tune Metalloelastase Specificity for Solubilized Elastin and Collagen Triple Helices

“…Mature elastin chains are cross-linked by desmosine linkages formed among most lysine residues (18,19). Elastin is "rubber-like," amorphous by x-ray fiber diffraction, and does not crystallize (20).…”

“…Mature elastin fibrils are insoluble, extensible, and intimately mingled with collagen, fibulin, other glycoproteins, and polysaccharides such as chondroitin sulfate (17)(18). Mature elastin chains are cross-linked by desmosine linkages formed among most lysine residues (18,19).…”

Perspectives on the Molecular and Biological Implications of Tropoelastin in Human Tissue Elasticity

“…[23] In contrast to the complex assembly of collagen type I, which relies on multiple proteolytic processing steps of the associating heterotrimer units, [25] tropoelastin is more amenable to study because its unprocessed monomers assemble on the path to elastin. [26] Multiple laboratories [27,28,29] have elegantly explored how microfibrils contribute to the distribution of elastin in vivo and that low-abundance molecules such as fibulins are needed for elastic fibre organization in vivo. [30] [31] Over the past few years, we and others have found that, in vitro, these molecules are not needed for the spatial and temporal elastin assembly of tropoelastin.…”

“…[42] The benefit of low thrombogenicity appears to be concentrated in a region from the N-terminus to domain 10 whereas endothelialization appears to be conferred by two autonomously functional regions: the central [43] and the C-terminus of tropoelastin. [44] Given the transient nature of tropoelastin in vivo before crosslinking into elastin, [27,45] these effects are presumably a feature of elastin or subregions within elastin. Tropoelastin elicits potent tropoelastin-promoted neoangiogenesis in mice and sheep and enhanced wound closure through accelerated epithelialization [46] but it is not yet known which part(s) of tropoelastin contribute(s) this effect, although endothelial cells recognize elastin by upregulating nitric oxide production by endothelial nitric oxide synthase through a phosphatidylinositol-4,5-bisphosphate 3-kinase pathway.…”