Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly

Sherratt, Michael J.; Wess, Tim J; Baldock, Clair; Ashworth, J.; Purslow, Peter P.; Shuttleworth, C. Adrian; Kielty, Cay M.

doi:10.1016/s0968-4328(99)00082-7

Cited by 80 publications

(71 citation statements)

References 62 publications

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“…Thus, other extracellular matrix aggregates, including basement membranes and microfibrils containing fibrillin (55) or collagen VI (56,57), are likely to be macromolecular alloys as well. It is even tempting to speculate that the concept applies to biological aggregates in general and, thus, may help to explain tissue-specific functions.…”

Section: Discussionmentioning

confidence: 99%

Macromolecular Specificity of Collagen Fibrillogenesis

Hansen

Brückner

2003

Journal of Biological Chemistry

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Suprastructures of the extracellular matrix, such as banded collagen fibrils, microfibrils, filaments, or networks, are composites comprising more than one type of macromolecule. The suprastructural diversity reflects tissue-specific requirements and is achieved by formation of macromolecular composites that often share their main molecular components alloyed with minor components. Both, the mechanisms of formation and the final macromolecular organizations depend on the identity of the components and their quantitative contribution. Collagen I is the predominant matrix constituent in many tissues and aggregates with other collagens and/or fibril-associated macromolecules into distinct types of banded fibrils. Here, we studied co-assembly of collagens I and XI, which co-exist in fibrils of several normal and pathologically altered tissues, including fibrous cartilage and bone, or osteoarthritic joints. Immediately upon initiation of fibrillogenesis, the proteins co-assembled into alloy-like stubby aggregates that represented efficient nucleation sites for the formation of composite fibrils. Propagation of fibrillogenesis occurred by exclusive accretion of collagen I to yield composite fibrils of highly variable diameters. Therefore, collagen I/XI fibrils strikingly differed from the homogeneous fibrillar alloy generated by collagens II and XI, although the constituent polypeptides of collagens I and II are highly homologous. Thus, the mode of aggregation of collagens into vastly diverse fibrillar composites is finely tuned by subtle differences in molecular structures through formation of macromolecular alloys.Extracellular matrix aggregates, despite their functional and morphological diversity, often contain the same type of macromolecules as their major constituent. In tendons, for example, large and strongly banded fibrils of variable width are aggregated into bundles that resist extreme tensile forces in one dimension. By contrast, thin fibrils with uniform diameter and spacing are organized into orthogonal sheets forming the translucent corneal stromal matrix that withstands high traction in two dimensions. However, the same protein, i.e. collagen I, is the quantitatively predominant component in both suprastructures (1, 2). The major cartilage collagen is type II, but this protein, too, is common to fibrils with different structures and functions (3, 4). Finally, collagens I and II occur together in fibrocartilage (5), a tissue characterized by a high resistance to both compressive and tensile forces and that contains fibrous bundles in addition to an amorphous extrafibrillar matrix rich in proteoglycans.Collagens I and II are very similar in their molecular structure. They both contain three polypeptides with a central sequence of 1014 amino acids in which strictly every third residue is glycine. In addition, these glycine residues are frequently preceded by hydroxyproline and/or followed by proline. The (Gly-Xaa-Yaa) n sequences are flanked at both ends by short non-periodic sequences, called telopeptide...

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Section: Discussionmentioning

confidence: 99%

Macromolecular Specificity of Collagen Fibrillogenesis

Hansen

Brückner

2003

Journal of Biological Chemistry

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“…Dimers can form between homologous regions of fibrillin, as well as between Nand C-terminal regions (24). Staining of microfibrils with monoclonal antibodies to fibrillin suggests that fibrillins are ordered in a head to tail parallel arrangement within microfibrils (7,25), which is supported by scanning transmission electron microscopy mass mapping and atomic force microscopy (26,27). Epitope mapping studies have suggested that stacking of fibrillin molecules within microfibrils occurs in an unstaggered arrangement (25).…”

mentioning

confidence: 91%

Microfibril-associated Glycoprotein-2 Interacts with Fibrillin-1 and Fibrillin-2 Suggesting a Role for MAGP-2 in Elastic Fiber Assembly

Penner

Rock

Kielty

et al. 2002

Journal of Biological Chemistry

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“…fibrillins and microfibril-associated glycoproteins (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Molecules of monomeric 70-kDa tropoelastin are synthesized by fibroblasts, chondrocytes, and smooth muscle cells and are secreted and properly aligned with one another for the subsequent lysyl oxidase-mediated cross-linking (12).…”

mentioning

confidence: 99%

Lysosomal Sialidase (Neuraminidase-1) Is Targeted to the Cell Surface in a Multiprotein Complex That Facilitates Elastic Fiber Assembly

Hinek

Pshezhetsky

Itzstein

et al. 2006

Journal of Biological Chemistry

146

140

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We have established previously that the 67-kDa elastin-binding protein (EBP), identical to the spliced variant of ␤-galactosidase, acts as a recyclable chaperone that facilitates secretion of tropoelastin. (Hinek, A., Keeley, F. W., and Callahan, J. W. (1995) Exp. Cell Res. 220, 312-324). We now demonstrate that EBP also forms a cell surfacetargeted molecular complex with protective protein/cathepsin A and sialidase (neuraminidase-1), and provide evidence that this sialidase activity is a prerequisite for the subsequent release of tropoelastin. We found that treatment with sialidase inhibitors repressed assembly of elastic fibers in cultures of human skin fibroblasts, aortic smooth muscle cells, and ear cartilage chondrocytes and caused impaired elastogenesis in developing chick embryos. Fibroblasts derived from patients with congenital sialidosis (primary deficiency of neuraminidase-1) and galactosialidosis (secondary deficiency of neuraminidase-1) demonstrated impaired elastogenesis, which could be reversed after their transduction with neuraminidase-1 cDNA or after treatment with bacterial sialidase, which has a similar substrate specificity to human neuraminidase-1. We postulate that neuraminidase-1 catalyzes removal of the terminal sialic acids from carbohydrate chains of microfibrillar glycoproteins and other adjacent matrix glycoconjugates, unmasking their penultimate galactosugars. In turn, the exposed galactosugars interact with the galectin domain of EBP, thereby inducing the release of transported tropoelastin molecules and facilitating their subsequent assembly into elastic fibers.Mature elastic fibers and laminae present in the extracellular matrix of connective tissues of different organs and blood vessel walls are complex structures made of polymeric (insoluble) elastin in which polypeptide chains of tropoelastin are covalently cross-linked and assembled on a scaffold of 12-nm microfibrils consisting of several glycoproteins, e.g. fibrillins and microfibril-associated glycoproteins (1-11). Molecules of monomeric 70-kDa tropoelastin are synthesized by fibroblasts, chondrocytes, and smooth muscle cells and are secreted and properly aligned with one another for the subsequent lysyl oxidase-mediated cross-linking (12). The mechanisms governing tropoelastin secretion and assembly are not fully elucidated. The current data indicate that highly hydrophobic and non-glycosylated tropoelastin associates with several intracellular proteins that chaperone it through the intracellular compartments. Davis et al. (13) documented that, in the ergastoplasmic reticulum, tropoelastin binds to BiP and the peptidylprolyl cis,transisomerase FKPB65. Our immunohistochemical and biochemical studies have indicated that tropoelastin present in endosomal and Golgi compartments is escorted by the 67-kDa elastin-binding protein (EBP) 2 (14, 15), which protects tropoelastin from premature intracellular selfaggregation and an association with serine proteinases (16,17). We have established that, after delivering tropoelastin to...

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Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and assembly

Cited by 80 publications

References 62 publications

Macromolecular Specificity of Collagen Fibrillogenesis

Macromolecular Specificity of Collagen Fibrillogenesis

Microfibril-associated Glycoprotein-2 Interacts with Fibrillin-1 and Fibrillin-2 Suggesting a Role for MAGP-2 in Elastic Fiber Assembly

Lysosomal Sialidase (Neuraminidase-1) Is Targeted to the Cell Surface in a Multiprotein Complex That Facilitates Elastic Fiber Assembly

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