Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linking

Baranova, Natalia S.; Inforzato, Antonio; Briggs, Deg; Tilakaratna, Viranga; Enghild, Jan J.; Thakar, Dhruv; Milner, Caroline M.; Day, Anthony J.; Richter, Ralf P.

doi:10.1074/jbc.m114.568154

Cited by 75 publications

(91 citation statements)

References 82 publications

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“…Evidently the positively charged histones can act as cross-linkers between the aggrecan molecules. Similar effects have been shown by cross-linkers in PCM model systems (71)(72)(73).…”

Section: Electrostatic Sequestration Of Positively Charged 20 Kda Molsupporting

confidence: 64%

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Chang

McLane

Fogg

et al. 2016

Biophysical Journal

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The hyaluronan-rich pericellular matrix (PCM) plays physical and chemical roles in biological processes ranging from brain plasticity, to adhesion-dependent phenomena such as cell migration, to the onset of cancer. This study investigates how the spatial distribution of the large negatively charged bottlebrush proteoglycan, aggrecan, impacts PCM morphology and cell surface access. The highly localized pericellular milieu limits transport of nanoparticles in a size-dependent fashion and sequesters positively charged molecules on the highly sulfated side chains of aggrecan. Both rat chondrocyte and human mesenchymal stem cell PCMs possess many unused binding sites for aggrecan, showing a 2.5x increase in PCM thickness from ∼7 to ∼18 μm when provided exogenous aggrecan. Yet, full extension of the PCM occurs well below aggrecan saturation. Hence, cells equipped with hyaluronan-rich PCM can in principle manipulate surface accessibility or sequestration of molecules by tuning the bottlebrush proteoglycan content to alter PCM porosity and the number of electrostatic binding sites.

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“…Evidently the positively charged histones can act as cross-linkers between the aggrecan molecules. Similar effects have been shown by cross-linkers in PCM model systems (71)(72)(73).…”

Section: Electrostatic Sequestration Of Positively Charged 20 Kda Molsupporting

confidence: 64%

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Chang

McLane

Fogg

et al. 2016

Biophysical Journal

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“…This is clearly a different mechanism from that identified here for CS. More similar is the binding of HA to TSG-6, which induces dimerization of the full-length protein, where this leads to crosslinking and a dramatic collapse and stiffening of the HA network 13, 16 . However, Link_TSG6 is not dimerized by HA, nor is its interaction with HA cooperative (as is the case for full-length TSG-6); it is the CUB module that likely mediates the protein-protein interaction between TSG-6 molecules 13 .…”

Section: Discussionmentioning

confidence: 99%

“…The interaction of TSG-6 with HA leads to the direct crosslinking and structural reorganization of the polysaccharide via HA-induced dimerization of TSG-6, which promotes the interaction of HA with its cell surface receptor CD44. Heparin can also dimerize the isolated Link module domain from human TSG-6, where this may regulate the activity of plasmin and thus the turnover of matrix 15 ; moreover, TSG-6 can mediate the crosslinking of structural proteins in the matrix 16 .…”

mentioning

confidence: 99%

Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6

et al. 2016

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Tumor necrosis factor-stimulated gene-6 (TSG-6) is a hyaluronan (HA) binding protein that is essential for stabilizing and remodelling the extracellular matrix (ECM) during ovulation and inflammatory disease processes such as arthritis. The Link module, one of the domains of TSG-6, is responsible for binding hyaluronan and other glycosaminoglycans (GAGs) found in the ECM. In this study, we used a well-defined chondroitin sulfate (CS) hexasaccharide (ΔC444S) to determine the structure of the Link module, in solution, in its chondroitin sulfate bound state. A variety of NMR techniques were employed, including chemical shift perturbation, residual dipolar couplings (RDCs), NOEs, spin relaxation measurements, and paramagnetic relaxation enhancements (PREs) from a spin-labeled analog of ΔC444S. The binding site for ΔC444S on the Link module overlapped with that of HA. Surprisingly, ΔC444S binding induced dimerization of the Link module (as confirmed by analytical ultracentrifugation), and a second weak binding site that partially overlapped with a previously identified heparin site was detected. A dimer model was generated using chemical shift perturbations and RDCs as restraints in the docking program HADDOCK. We postulate that the molecular cross-linking enhanced by the multiple binding modes of the Link module may be critical for remodeling the ECM during inflammation/ovulation and may contribute to other functions of TSG-6.

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“…This matrix consists mostly of the glycosaminoglycan, hyaluronan (HA), as well as HA-binding proteins (Chen et al 1996;Fulop et al 1997a;Hess et al 1998;Sato et al 2001;Yoshioka et al 2000) and proteoglycans (McArthur et al 2000) that maintain the stability and structure of the matrix. The integrity of the mucified matrix also requires proteins such as pentraxin 3 (PTX3) and tumor necrosis factor-inducible gene 6 (TNFAIP6) (Baranova et al 2014;Fulop et al 2003;Ievoli et al 2011;Salustri et al 2004;Sanggaard et al 2008;Scarchilli et al 2007) which mediate the interactions between the components of the matrix. These factors, along with other proteins that are needed for cumulus expansion including Ptgs2 (prostaglandin-endoperoxide synthase 2) (Davis et al 1999;Ochsner et al 2003b;Sirois et al 1992), hyaluronan synthase Fig.…”

Section: Cumulus Expansionmentioning

confidence: 98%

Control of Oocyte Growth and Development by Intercellular Communication Within the Follicular Niche

El‐Hayek

Clarke

2016

Results and Problems in Cell Differentiation

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In the mammalian ovary, each oocyte grows and develops within its own structural and developmental niche-the follicle. Together with the female germ cell in the follicle are somatic granulosa cells, specialized companion cells that surround the oocyte and provide support to it, and an outer layer of thecal cells that serve crucial roles including steroid synthesis. These follicular compartments function as a single physiological unit whose purpose is to produce a healthy egg, which upon ovulation can be fertilized and give rise to a healthy embryo, thus enabling the female germ cell to fulfill its reproductive potential. Beginning from the initial stage of follicle formation and until terminal differentiation at ovulation, oocyte and follicle growth depend absolutely on cooperation between the different cellular compartments. This cooperation synchronizes the initiation of oocyte growth with follicle activation. During growth, it enables metabolic support for the follicle-enclosed oocyte and allows the follicle to fulfill its steroidogenic potential. Near the end of the growth period, intra-follicular interactions prevent the precocious meiotic resumption of the oocyte and ensure its nuclear differentiation. Finally, cooperation enables the events of ovulation, including meiotic maturation of the oocyte and expansion of the cumulus granulosa cells. In this chapter, we discuss the cellular interactions that enable the growing follicle to produce a healthy oocyte, focusing on the communication between the germ cell and the surrounding granulosa cells.

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Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linking

Cited by 75 publications

References 82 publications

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Cell Surface Access Is Modulated by Tethered Bottlebrush Proteoglycans

Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6

Control of Oocyte Growth and Development by Intercellular Communication Within the Follicular Niche

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