R-spondins are BMP receptor antagonists in Xenopus early embryonic development
| العنوان: | R-spondins are BMP receptor antagonists in Xenopus early embryonic development |
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| المؤلفون: | Andrey Glinka, Hyeyoon Lee, Rui Sun, Carina Seidl, Christof Niehrs |
| المصدر: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, animal structures, Science, Ubiquitin-Protein Ligases, Xenopus, Embryonic Development, General Physics and Astronomy, Bone Morphogenetic Protein 4, Xenopus Proteins, Ligands, Article, General Biochemistry, Genetics and Molecular Biology, Xenopus laevis, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Cell Line, Tumor, Membrane proteins, Developmental biology, Animals, Humans, lcsh:Science, Receptor, RSPO2, Bone Morphogenetic Protein Receptors, Type I, In Situ Hybridization, Tissue homeostasis, Multidisciplinary, biology, Chemistry, Synexpression, Wnt signaling pathway, Gene Expression Regulation, Developmental, General Chemistry, biology.organism_classification, BMPR1A, Cell biology, Wnt Proteins, 030104 developmental biology, embryonic structures, Intercellular Signaling Peptides and Proteins, lcsh:Q, Stem cell, Thrombospondins, 030217 neurology & neurosurgery, Signal Transduction, Cell signalling |
| الوصف: | BMP signaling plays key roles in development, stem cells, adult tissue homeostasis, and disease. How BMP receptors are extracellularly modulated and in which physiological context, is therefore of prime importance. R-spondins (RSPOs) are a small family of secreted proteins that co-activate WNT signaling and function as potent stem cell effectors and oncogenes. Evidence is mounting that RSPOs act WNT-independently but how and in which physiological processes remains enigmatic. Here we show that RSPO2 and RSPO3 also act as BMP antagonists. RSPO2 is a high affinity ligand for the type I BMP receptor BMPR1A/ALK3, and it engages ZNRF3 to trigger internalization and degradation of BMPR1A. In early Xenopus embryos, Rspo2 is a negative feedback inhibitor in the BMP4 synexpression group and regulates dorsoventral axis formation. We conclude that R-spondins are bifunctional ligands, which activate WNT- and inhibit BMP signaling via ZNRF3, with implications for development and cancer. R-spondins are known modulators of Wnt signaling. Here, the authors demonstrate that R-spondins function in Xenopus embryonic development as BMP antagonists by targeting BMP receptor 1A for degradation. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::970268727c5fdf4537b4e06bdc1f6e98 https://doi.org/10.1038/s41467-020-19373-w |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....970268727c5fdf4537b4e06bdc1f6e98 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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