The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate
<p>Abstract</p> <p>Background</p> <p>Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold...
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| Format: | Article |
| Language: | English |
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BMC
2008-08-01
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| Series: | Neural Development |
| Online Access: | http://www.neuraldevelopment.com/content/3/1/19 |
| _version_ | 1811251198583373824 |
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| author | Esteve Pilar Lopez-Rios Javier Ruiz Jose Bovolenta Paola |
| author_facet | Esteve Pilar Lopez-Rios Javier Ruiz Jose Bovolenta Paola |
| author_sort | Esteve Pilar |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (Sfrp<sub>CRD</sub>) related to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin module (Sfrp<sub>NTR</sub>) defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that Sfrp<sub>CRD </sub>interferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the Sfrp<sub>NTR </sub>has been barely addressed.</p> <p>Results</p> <p>Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1<sub>NTR </sub>mimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1<sub>NTR</sub>. In contrast, the Sfrp1<sub>CRD </sub>cannot mirror the function of the entire molecule <it>in vivo </it>but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity.</p> <p>Conclusion</p> <p>On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.</p> |
| first_indexed | 2024-04-12T16:16:03Z |
| format | Article |
| id | doaj.art-000aeef8eae84b809f681a4c952ecdae |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-04-12T16:16:03Z |
| publishDate | 2008-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-000aeef8eae84b809f681a4c952ecdae2022-12-22T03:25:43ZengBMCNeural Development1749-81042008-08-01311910.1186/1749-8104-3-19The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plateEsteve PilarLopez-Rios JavierRuiz JoseBovolenta Paola<p>Abstract</p> <p>Background</p> <p>Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (Sfrp<sub>CRD</sub>) related to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin module (Sfrp<sub>NTR</sub>) defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that Sfrp<sub>CRD </sub>interferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the Sfrp<sub>NTR </sub>has been barely addressed.</p> <p>Results</p> <p>Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1<sub>NTR </sub>mimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1<sub>NTR</sub>. In contrast, the Sfrp1<sub>CRD </sub>cannot mirror the function of the entire molecule <it>in vivo </it>but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity.</p> <p>Conclusion</p> <p>On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.</p>http://www.neuraldevelopment.com/content/3/1/19 |
| spellingShingle | Esteve Pilar Lopez-Rios Javier Ruiz Jose Bovolenta Paola The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate Neural Development |
| title | The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate |
| title_full | The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate |
| title_fullStr | The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate |
| title_full_unstemmed | The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate |
| title_short | The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate |
| title_sort | netrin related domain of sfrp1 interacts with wnt ligands and antagonizes their activity in the anterior neural plate |
| url | http://www.neuraldevelopment.com/content/3/1/19 |
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