Evidence of a defined spatial arrangement of hyaluronate in the central filament of cartilage proteoglycan aggregates

Mörgelin, Matthias; Paulsson, Mats; Aebi, Ueli; Engel, Jürgen

doi:10.1042/bj3070595

Cited by 49 publications

(43 citation statements)

References 41 publications

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“…In electron micrographs one sees fine thread-like structures (Fig. 8) that extend laterally from the core protein and are consistent in appearance with that of glycosaminoglycan chains visualized in other proteoglycans (35,36). Although these appear to arise from sites throughout the core protein, some of those seen near the globular region may in fact represent chondroitin sulfate chains with attachment sites in the C-terminal half of the proteoglycan but that follow the core protein before reaching out into the surrounding space (as has been observed previously in the case of aggrecan (35)).…”

Section: Discussionmentioning

confidence: 99%

The Fibrinogen-like Globe of Tenascin-C Mediates Its Interactions with Neurocan and Phosphacan/Protein-tyrosine Phosphatase-ζ/β

Milev¹,

Fischer²,

Häring³

et al. 1997

Journal of Biological Chemistry

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Two nervous tissue-specific chondroitin sulfate proteoglycans, neurocan and phosphacan (the extracellular domain of protein-tyrosine phosphatase-/␤), are highaffinity ligands of tenascin-C. Using portions of tenascin-C expressed as recombinant proteins in human fibrosarcoma cells, we have demonstrated both by direct radioligand binding assays and inhibition studies that phosphacan binding is retained in all deletion variants except those lacking the fibrinogen-like globe and that phosphacan binds to this single domain with nearly the same affinity (K d ϳ12 nM) as to native or recombinant tenascin-C. However, maximum binding of neurocan requires both the fibrinogen globe and some of the adjacent fibronectin type III repeats. Binding of phosphacan and neurocan to intact tenascin-C, and of phosphacan to the fibrinogen globe, is significantly increased in the presence of calcium. Chondroitinase treatment of the proteoglycans did not affect their binding to either native tenascin-C or to any of the recombinant proteins, demonstrating that these interactions are mediated by the proteoglycan core proteins rather than through the glycosaminoglycan chains. These results are also consistent with rotary shadowing electron micrographs that show phosphacan as a rod terminated at one end by a globular domain that is frequently seen apposed to the fibrinogen globe in mixtures of phosphacan and tenascin-C. C6 glioma cells adhere to and spread on deletion variants of tenascin-C containing only the epidermal growth factor-like domains or the fibronectin type III repeats and the fibrinogen globe. In both cases cell adhesion was inhibited by similar concentrations of phosphacan, demonstrating that the fibrinogen globe is not necessary for this effect, which is apparently mediated by a direct action of phosphacan on the cells rather than by its interaction with the proteoglycan binding site on tenascin-C.We have previously reported that neurocan and phosphacan/ protein-tyrosine phosphatase-/␤, two major nervous tissuespecific chondroitin sulfate proteoglycans, are high affinity ligands of tenascin-C (apparent K d ϳ3 nM) and that phosphacan inhibits the adhesion of C6 glioma cells to tenascin-C (1). Neurocan is a multidomain proteoglycan with a 136-kDa core protein (2) and together with versican and brevican is a member of the aggrecan family of hyaluronan-binding proteoglycans (3). It contains N-terminal immunoglobulin-like and hyaluronanbinding domains, a C-terminal domain consisting of EGF-, lectin-, and complement regulatory protein-like sequences, and a nonhomologous central domain of 593 amino acids, which contains the attachment sites for the three chondroitin sulfate chains and a large number of O-glycosidic oligosaccharides. In contrast, phosphacan (4, 5), which contains a 173-kDa core protein and three chondroitin sulfate chains, is an mRNA splicing product that represents the entire extracellular domain of a receptor-type protein-tyrosine phosphatase that also occurs as a chondroitin sulfate proteoglycan in brain (3). Phos...

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Section: Discussionmentioning

confidence: 99%

The Fibrinogen-like Globe of Tenascin-C Mediates Its Interactions with Neurocan and Phosphacan/Protein-tyrosine Phosphatase-ζ/β

Milev¹,

Fischer²,

Häring³

et al. 1997

Journal of Biological Chemistry

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“…Thus, the osmotic swelling pressure of the pericellular matrix is increased when more proteoglycan is present. The presence of proteoglycans would also act to stiffen a network of hyaluronan by effectively shortening the hyaluronan chain as it wraps around the globular G1 domain [17]. When excess proteoglycan is added to the coat, the pore size of the pericellular matrix is decreased, with particles 0.3 microns or larger excluded [18].…”

Section: Pericellular Matrix Structurementioning

confidence: 99%

“…When excess proteoglycan is added to the coat, the pore size of the pericellular matrix is decreased, with particles 0.3 microns or larger excluded [18]. Link proteins stabilize the interaction between hyaluronic acid and proteoglycans [19][20][21] and have been shown to have a shortening effect on the length of hyaluronan that is similar to the proteoglycan [17]. Others have shown that adding an excess of link proteins can cause fragmentation or disruption of hyaluronan networks [22].…”

Section: Pericellular Matrix Structurementioning

confidence: 99%

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

259

238

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Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

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“…sist of an alternating array of cLP and aggrecan molecules along a central hyaluronan filament (20). Therefore, aggregates (potentially containing new members of the HAPLN family) in which other CSPGs substitute for aggrecan might contribute to the structural integrity of many different tissues.…”

mentioning

confidence: 99%

Expression and Purification of Functionally Active Hyaluronan-binding Domains from Human Cartilage Link Protein, Aggrecan and Versican

Seyfried

McVey

Almond

et al. 2005

Journal of Biological Chemistry

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The chondroitin sulfate proteoglycan aggrecan forms link protein-stabilized complexes with hyaluronan (HA), via its N-terminal G1-domain, that provide cartilage with its load bearing properties. Similar aggregates (potentially containing new members of the link protein family), in which other chondroitin sulfate proteoglycans (i.e. versican, brevican, and neurocan) substitute for aggrecan, may contribute to the structural integrity of many other tissues including skin and brain. In this study, cartilage link protein (cLP) and the G1-domains of aggrecan (AG1) and versican (VG1) were expressed in Drosophila S2 cells. The recombinant human proteins were found to have properties similar to those described for the native molecules (e.g. cLP was able to form oligomers, and HA decasaccharides were the minimum size that could compete effectively for their binding to polymeric HA). Gel filtration and protein cross-linking/ matrix-assisted laser desorption ionization time-offlight peptide fingerprinting showed that cLP and AG1 interact in the absence or presence of HA. Conversely, cLP and VG1 did not bind directly to each other in solution yet formed ternary complexes with HA24. Nlinked glycosylation of AG1 and VG1 was demonstrated to be unnecessary for either HA binding or the formation of ternary complexes. Surprisingly, the length of HA required to accommodate two G1-domains was found to be significantly larger for aggrecan than versican, which may reflect differences in the conformation of HA stabilized on binding these proteins.

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Evidence of a defined spatial arrangement of hyaluronate in the central filament of cartilage proteoglycan aggregates

Cited by 49 publications

References 41 publications

The Fibrinogen-like Globe of Tenascin-C Mediates Its Interactions with Neurocan and Phosphacan/Protein-tyrosine Phosphatase-ζ/β

The Fibrinogen-like Globe of Tenascin-C Mediates Its Interactions with Neurocan and Phosphacan/Protein-tyrosine Phosphatase-ζ/β

Hyaluronan-dependent pericellular matrix☆

Expression and Purification of Functionally Active Hyaluronan-binding Domains from Human Cartilage Link Protein, Aggrecan and Versican

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