Interaction of Tropoelastin with the Amino-terminal Domains of Fibrillin-1 and Fibrillin-2 Suggests a Role for the Fibrillins in Elastic Fiber Assembly

Trask, Timothy M.; Trask, Barbara Crippes; Ritty, Timothy M.; Abrams, William R.; Rosenbloom, Joel; Mecham, Robert P.

doi:10.1074/jbc.m003665200

Cited by 125 publications

(112 citation statements)

References 35 publications

(37 reference statements)

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“…The specific complexing of biglycan to MAGP-1 and tropoelastin suggests that biglycan may also be involved in this process. However, recent evidence indicates that tropoelastin can bind directly to the fibrillin-1 component of the microfibrils, suggesting that elastin deposition may occur independently of MAGP-1 (40). In addition, it has recently been shown that biglycan null mice have no obvious disturbance of elastic fiber assembly (8), suggesting that any role for biglycan in this process is likely to be limited.…”

Section: Discussionmentioning

confidence: 99%

Molecular Interactions of Biglycan and Decorin with Elastic Fiber Components

Reinboth

Hanssen

Cleary

et al. 2002

Journal of Biological Chemistry

144

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The interactions of the dermatan sulfate proteoglycans biglycan and decorin have been investigated with the elastic fiber components, tropoelastin, fibrillin-containing microfibrils, and microfibril-associated glycoproteins (MAGP) 1 and 2. Both proteoglycans were found to bind tropoelastin and fibrillin-containing microfibrils but not MAGPs 1 and 2 in solid phase binding assays. The specificity of the binding of biglycan and decorin to tropoelastin was confirmed by co-immunoprecipitation experiments and by the blocking of the interactions with elastin-derived peptides. Isolated core proteins from biglycan and decorin bound to tropoelastin more strongly than the intact proteoglycans, and there were no differences in the tropoelastin binding characteristics of distinct glucuronate-rich and iduronate-rich glycoforms of biglycan. These findings indicated that the binding sites were contained in the protein cores of the proteoglycans rather than the glycosaminoglycan side chains. Scatchard analysis showed that biglycan bound more avidly than decorin to tropoelastin with K d values estimated as 1.95 ؋ 10 ؊7 M and 5.3 ؋ 10 ؊7 M, respectively. In blocking experiments each proteoglycan showed extensive inhibition of binding of the other to tropoelastin but was most effective at blocking its own binding. This result suggested that biglycan and decorin had closely spaced but distinct binding sites on tropoelastin. Addition of the elastin-binding protein MAGP-1 to the assays enhanced the binding of biglycan to tropoelastin but had no effect on the decorin-tropoelastin interaction. Co-immunoprecipitation experiments showed that MAGP-1 interacted with biglycan but not decorin in the solution phase. The results indicated that biglycan specifically formed a ternary complex with tropoelastin and MAGP-1. Overall the study supports the concept that biglycan may have a specific role in the elastinogenic phase of elastic fiber formation.

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Section: Discussionmentioning

confidence: 99%

Molecular Interactions of Biglycan and Decorin with Elastic Fiber Components

Reinboth

Hanssen

Cleary

et al. 2002

Journal of Biological Chemistry

144

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“…The addition of elastin is an evolutionary adaptation in vertebrate animals to handle the high pulsatile pressures of a closed circulatory system (Faury, 2001). Fibrillin-1 and -2 bind tropoelastin in solid phase binding assays (Trask et al, 2000b).…”

Section: Fibrillinsmentioning

confidence: 99%

New insights into elastic fiber assembly

Wagenseil

Mecham

2007

Birth Defects Research Pt C

Self Cite

345

354

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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,

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“…However, other studies (32) have indicated that although MAGP-1 can bind intact tropoelastin, N-and C-terminal halves of elastin generated by proteolytic digestion are unable to bind MAGP-1 alone, suggesting a complex mechanism of interaction. Both fibrillin-1 and fibrillin-2 interact with tropoelastin through a region near the N terminus of fibrillin (33). Chondroitin sulfate proteoglycans have been shown to associate with fibrillin at the beads, with chondroitinase treatment disrupting the bead structure (34).…”

mentioning

confidence: 99%