Molecular Interactions of Biglycan and Decorin with Elastic Fiber Components

Reinboth, Betty; Hanssen, Eric; Cleary, Eimear; Gibson, Mark

doi:10.1074/jbc.m109540200

Cited by 146 publications

(75 citation statements)

References 39 publications

(46 reference statements)

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“…Consistent with this hypothesis is the observation that only a portion of versican, a large chondroitin sulfate proteoglycan that associates with microfibrils, remains bound to the microfibrils following their extraction from human fetal membranes using crude collagenase (Isogai et al, 2002). In addition to versican, two smaller proteoglycans, biglycan and decorin, have also been shown to interact with microfibrils (Reinboth et al, 2002;Trask et al, 2000). The extent to which these proteins, and the many other proteins that have been localized to microfibrils, contribute to the microfibril substructure remains to be determined.…”

Section: Discussionsupporting

confidence: 52%

Ultrastructural properties of ciliary zonule microfibrils

Davis¹

2002

Journal of Structural Biology

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Conventional electron microscopy and rotary shadowing techniques have provided conflicting interpretations of microfibril ultrastructure. To address this issue, we have used quick-freeze deep-etch (QFDE) microscopy to obtain 3-dimensional surface views of microfibrils that have not been fixed, dehydrated, or stained with heavy metals. By this approach, microfibrils appear as tightly packed rows of bead-like subunits that do not display the interbead filamentous links seen by other methods. At regular 50-nm intervals along the microfibril length, a larger bead is often recognized which tends to be aligned with those from adjacent microfibrils when the microfibrils are in bundles. This evidence of organized lateral associations of microfibrils is supported by the observation of small filaments that span between the adjacent microfibrils. When QFDE microscopy was used to examine microfibrils exposed to sonication, partially dissociated microfibrils with the more typical ''beads on a string'' appearance were observed. Beads are also seen alone, as monomers, often with an array of small thread-like filaments extending from the bead in a ''crab-like'' manner. Our results suggest that the beads on a string appearance of sonicated microfibrils may result from a partial loss of protein components from the interbead domains, thus leading to exposure of a filamentous substructure. It is possible, therefore, that this phenomenon might also contribute to the beads on a string appearance of microfibrils seen using other electron microscopy techniques.

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Section: Discussionsupporting

confidence: 52%

Ultrastructural properties of ciliary zonule microfibrils

Davis¹

2002

Journal of Structural Biology

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“…Tropoelastin was shown to bind a fibrillin-1 fragment (encoded by exons 10 -17) through interactions involving its lysine side chains (14). Ternary complexes of MAGP-1, fibrillin, and decorin and of MAGP-1, tropoelastin, and biglycan have been identified in vitro (15,16). Whereas small leucine-rich proteoglycans may contribute to elastic fiber formation, available evidence indicates that the key molecules in this process are tropoelastin, fibrillin-1, and MAGP-1.…”

mentioning

confidence: 99%

Molecular Basis of Elastic Fiber Formation

Rock

Cain

Freeman

et al. 2004

Journal of Biological Chemistry

144

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We have investigated the molecular basis of elastic fiber formation on fibrillin microfibrils. Binding assays revealed high affinity calcium-independent binding of two overlapping fibrillin-1 fragments (encoded by central exons 18 -25 and 24 -30) to tropoelastin, which, in microfibrils, map to an exposed "arms" feature adjacent to the beads. A further binding site within an adjacent fragment (encoded by exons 9 -17) was within an eightcysteine motif designated TB2 (encoded by exons 16 and 17). Binding to TB2 was ablated by the presence of Nterminal domains (encoded by exons 1-8) and reduced after deleting the proline-rich region. A novel transglutaminase cross-link between tropoelastin and fibrillin-1 fragment (encoded by exons 9 -17) was localized by mass spectrometry to a sequence encoded by exon 17. The high affinity binding and cross-linking of tropoelastin to a central fibrillin-1 sequence confirm that this association is fundamental to elastic fiber formation. Microfibril-associated glycoprotein-1 showed calcium-dependent binding of moderate affinity to fibrillin-1 N-terminal fragment (encoded by exons 1-8), which localize to the beads. Microfibril-associated glycoprotein-1 thus contributes to microfibril organization but may also form secondary interactions with adjacent microfibril-bound tropoelastin.

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“…The C-terminal half contains all of the molecule's thirteen cysteine residues and encodes a 54-amino acid sequence that defines a matrix-binding domain that targets MAGP-1 to the ECM. MAGP-1 binds to tropoelastin and type VI collagen (11,12) and interacts with other molecules with defined structural roles in the ECM such as fibrillin-1 and -2 (13,14), decorin (15), and biglycan (16). It does not, however, bind to the interstitial collagens I, III, or V (12).…”

mentioning

confidence: 99%

Deficiency in Microfibril-associated Glycoprotein-1 Leads to Complex Phenotypes in Multiple Organ Systems

Weinbaum

Broekelmann

Pierce

et al. 2008

Journal of Biological Chemistry

134

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Microfibril-associated glycoprotein-1 (MAGP-1) is a small molecular weight component of the fibrillin-rich microfibril. Gene-targeted inactivation of MAGP-1 reveals a complex phenotype that includes increased body weight and size due to excess body fat, an altered wound healing response in bone and skin, and a bleeding diathesis. Elastic tissues rich in MAGP-1-containing microfibrils develop normally and show normal function. The penetrance of MAGP-1-null phenotypes is highly variable and mouse strain-dependent, suggesting the influence of modifier genes. MAGP-1 was found to bind active transforming growth factor-␤ (TGF-␤) and BMP-7 with high affinity, suggesting that it may be an important modulator of microfibrilmediated growth factor signaling. Many of the phenotypic traits observed in MAGP-1-deficient mice are consistent with loss of TGF-␤ function and are generally opposite those associated with mutations in fibrillin-1 that result in enhanced TGF-␤ signaling. Increased body size and fat deposition in MAGP-1-mutant animals are particularly intriguing given the localization of obesity traits in humans to the region on chromosome 1 containing the MAGP-1 gene.Microfibrils are important contributors to the structural integrity of tissues and participate in the assembly of elastic fibers during development. They also serve to bind and sequester growth factors in the extracellular matrix (ECM) 3 (1, 2) and can directly signal cells through sequence motifs that interact with integrins and other cell-surface receptors (3-6). The major structural components of these microfibrils are the fibrillins, large glycoproteins rich in calcium binding epidermal growth factor-like domains (7), and the MAGPs, small, cysteine-rich proteins of unknown function. Other proteins can be localized to microfibrils, but it is not clear whether they are integral or associated proteins (8).MAGP-1, a ϳ20-kDa glycoprotein, is synthesized by most matrix-producing cells (9). The N-terminal half of the molecule contains sites for tyrosine sulfation and transglutaminase crosslinking as well as all of the tri-and tetrasaccharide O-linked sugars (10). The first 20 amino acids of the protein are enriched in acidic residues that, together with the sulfotyrosines, create a region of high negative charge capable of binding cationic proteins. The C-terminal half contains all of the molecule's thirteen cysteine residues and encodes a 54-amino acid sequence that defines a matrix-binding domain that targets MAGP-1 to the ECM. MAGP-1 binds to tropoelastin and type VI collagen (11, 12) and interacts with other molecules with defined structural roles in the ECM such as fibrillin-1 and -2 (13, 14), decorin (15), and biglycan (16). It does not, however, bind to the interstitial collagens I, III, or V (12). MAGP-1 also interacts with and facilitates the shedding of Notch1 (17), but there is no evidence for interaction with integrins.MAGP-2 is the other member of the MAGP family and, like MAGP-1, is covalently associated with fibrillin-containing microfibrils (...

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Molecular Interactions of Biglycan and Decorin with Elastic Fiber Components

Cited by 146 publications

References 39 publications

Ultrastructural properties of ciliary zonule microfibrils

Ultrastructural properties of ciliary zonule microfibrils

Molecular Basis of Elastic Fiber Formation

Deficiency in Microfibril-associated Glycoprotein-1 Leads to Complex Phenotypes in Multiple Organ Systems

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