Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix

Briggs, Deg; Birchenough, Holly L.; Ali, Tariq; Rugg, Marilyn S.; Waltho, Jonathan P.; Ievoli, Elena; Jowitt, Thomas A.; Enghild, Jan J.; Richter, Ralf P.; Salustri, Antonietta; Milner, Caroline M.; Day, Anthony J.

doi:10.1074/jbc.m115.669838

Cited by 52 publications

(88 citation statements)

References 96 publications

(197 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These extend upward from the cleft between monomers seen in Figure 7. A crystal structure of the CUB domain has recently been published 79 , and without altering the structure of either domain we have been able to dock a pair of CUB modules to these termini with a minimal clash of surface residues (Supplementary Figure S7). The CUB modules are in close proximity to one another allowing for possible additional interactions in the context of a TSG-6 dimer.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, there is evidence that the binding of TSG-6 to CS is involved in HC•TSG-6 formation 22, 29, 85 . Thus, HC transfer might potentially involve dimerization of TSG-6 via its binding to CS facilitating a subsequent transfer of HC to HA bound to a second TSG-6 molecule.…”

Section: Discussionmentioning

confidence: 99%

“…The transfer of HCs onto HA likely involves the interaction of TSG-6 with the CS chain of IαI, i.e. during the formation of the HC•TSG-6 intermediate 22, 29 .…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…PTGS2 is the prostaglandin ratelimiting enzyme, and prostaglandin signaling is crucial for the assembly of the cumulus matrix (Davis et al, 1999;Hizaki et al, 1999). PTX3 and TNFAIP6 stabilize hyaluronan to maintain the expanded matrix (Briggs et al, 2015;Richards, 2005;Salustri et al, 2004;Varani et al, 2002). Null mutations in Ptgs2, Ptx3, or Tnfaip6 genes or inhibition of HAS2 activity causes no or defective cumulus expansion (Chen et al, 1993;Fulop et al, 2003;Ochsner et al, 2003;Varani et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

CREB activity is required for epidermal growth factor‐induced mouse cumulus expansion

Yang

et al. 2019

Molecular Reproduction Devel

View full text Add to dashboard Cite

The release of a fertilizable oocyte from the ovary is dependent upon the expansion of the cumulus cells. The expansion requires cooperation between epidermal growth factor (EGF) family peptide‐activated mitogen‐activated protein kinase (MAPK)3/1 and oocyte paracrine factor‐activated‐Sma‐ and Mad‐related protein (SMAD)2/3 signaling in cumulus cells. However, the mechanism underlying (MAPK)3/1 signaling is unclear. In the present study, the EGF‐activation of EGF receptor (EGFR) induced cyclic adenosine 3′,5′‐monophosphate (cAMP) response element‐binding protein (CREB) phosphorylation in cumulus cells, and the interruption of CREB functional complex formation by naphthol AS‐E phosphate (KG‐501) completely blocked the EGF‐stimulated expansion‐related gene expression. EGF‐stimulated phosphorylation of CREB was completely inhibited by MAPK3/1 inhibitor U0126, suggesting that EGF‐activated MAPK3/1 results in the activation of CREB for cumulus expansion. Also, the role of EGF‐stimulated calcium signaling was studied. Calcium‐elevating reagents ionomycin and sphingosine‐1‐phosphate mimicked, but calcium chelators bis‐(o'aminophenoxy)‐ethane‐N,N,N,N‐tetraacetic acid, tetra(acetoxymethyl)‐ester, and 8‐(N,N‐diethylamino)‐octyl‐3,4,5‐trimethoxybenzoate abolished the activity of EGF on CREB phosphorylation, cumulus expansion, and expansion‐related gene expression. Furthermore, EGF‐induced cumulus expansion was inhibited by calmodulin (CaM)‐dependent protein kinase II (CaMKII) inhibitors, KN‐93 and autocamtide‐2‐related inhibitory peptide. However, the inhibition of SMAD2/3 activity by removal of oocyte from cumulus–oocyte complexes did not affect the EGF‐induced CREB phosphorylation, indicating that EGF‐activated CREB is independent of oocyte‐activated SMAD2/3 signaling. Therefore, EGF‐induced CREB activity by MAPK3/1 and Ca2+/CaMKII signaling pathways promotes the expansion‐related gene expression and consequent cumulus expansion.

show abstract

“…In some contexts, HC•HAs can be crosslinked by the binding of HCs to the octameric protein pentraxin-3 (PTX3) (Baranova et al, 2014), where, for example, the multivalent nature of PTX3 is essential to the stabilisation of the cumulus matrix (Inforzato et al, 2008). Either deletion of PTX3, or loss/impairment of TSG-6’s HC transferase activity in mice, also leads to the failure of COC expansion and, hence, infertility (Briggs et al, 2015; Fülöp et al, 2003; Ochsner et al, 2003; Salustri et al, 2004). Here the cooperation between HA, IαI, PTX3 and TSG-6 (Baranova et al, 2014) leads to the formation of an elastic tissue, which is the softest described to date with a Young’s modulus on the order of 1Pa (Chen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Heavy chain-1 of inter-α-inhibitor has an integrin-like structure with immune regulatory activities

Briggs

Langford-Smith

Jowitt

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

16Inter-α-inhibitor (IαI) 1 is a proteoglycan essential for mammalian reproduction that also plays a less well-17 characterised role in inflammation. IαI is composed of 2 homologous 'heavy chains ' (HC1 and HC2) 18 covalently attached to chondroitin sulphate on the bikunin core protein. Prior to ovulation HCs are 19 transferred onto the polysaccharide hyaluronan (HA), thereby stabilising a matrix that is required for 20 fertilisation. Here we show that human HC1 has a structure similar to integrin β-chains and contains a 21 functional MIDAS (metal ion-dependent adhesion site) motif that can mediate self-association of heavy 22 chains, providing a mechanism for matrix crosslinking. Surprisingly, its interaction with RGD-containing 23 integrin ligands, such as vitronectin and the latency-associated peptides of TGFβ, occurs in a MIDAS/cation-24 independent manner. However, HC1 utilises its MIDAS motif to bind to, and inhibit the cleavage of, 25 complement C3, thus identifying it as a novel regulator of innate immunity through inhibition of the 26 alternative pathway C3 convertase. 27 28 1 Abbreviations 29 ADPs, atomic displacement parameter; AUC, analytical ultracentrifugation; CMG2, capillary morphogenesis 30 protein-2; COC, cumulus-oocyte complex; CS, chondroitin sulphate; FB, complement factor B; FnIII; 31 fibronectin type III; HA, hyaluronan; HC, heavy chain; HC•HA, covalent complex of HC with HA; IαI, 32 inter-α-inhibitor; ITGA, integrin α-chain; ITGB, integrin β-chain; LAP, latency associated peptide; LLC, 33 large latent complex; LTBP, latent TGFβ binding protein; MIDAS, metal ion-dependent adhesion site; PαI, 34 pre-α-inhibitor; PTX3, pentraxin-3; rHC1, recombinant HC1; SAXS, small-angle X-ray scattering; SHAP, 35 serum-derived HA binding protein; SLC, small latent complex; TEM8, tumour endothelial marker-8; TGFβ, 36 transforming factor β; TSG-6, tumour necrosis factor-stimulated gene-6; TSG-6•HC, covalent complex of 37 TSG-6 and HC; vWFA domain, von Willebrand Factor A domain. 29 to form HC•HA (aka SHAP-HA) complexes (Day and Milner, 2019; Rugg et al., 2005). TSG-6 also 30 mediates the formation of HC•HAs during inflammation, when IαI/PαI leak into tissues from the circulation. 31 32 The covalent attachment of HCs changes the physical properties of HA. For example in synovial fluid from 33 rheumatoid arthritis patients, where on average 3 to 5 HCs are attached to an HA chain of ~2 MDa, the 34 polysaccharide is more aggregated compared to unmodified HA (Yingsung et al., 2003); this has been 35 attributed to crosslinking of HC•HA complexes via interactions between HCs based on their apparent 36 associations visualised by electron microscopy. Given that HC1, HC2 and HC3 can all be transferred onto 37 HA during arthritis (Zhao et al., 1995) such crosslinking could be mediated by homotypic and/or heterotypic

show abstract

Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix

Cited by 52 publications

References 96 publications

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

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

CREB activity is required for epidermal growth factor‐induced mouse cumulus expansion

Heavy chain-1 of inter-α-inhibitor has an integrin-like structure with immune regulatory activities

Contact Info

Product

Resources

About