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Nat Commun 2020 Nov 04;111:5570. doi: 10.1038/s41467-020-19373-w.
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R-spondins are BMP receptor antagonists in Xenopus early embryonic development.

Lee H , Seidl C , Sun R , Glinka A , Niehrs C .

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.

PubMed ID: 33149137
PMC ID: PMC7642414
Article link: Nat Commun

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: acvr1 babam2 bmp4 bmpr1a bmpr1b chrd crisp1.3 dsp foxg1 furin lgr4 lrp6 myod1 nppa rspo1 rspo2 rspo3 smad1 szl tf ventx1.2 wnt3a znrf3
GO keywords: dorsal/ventral axis specification [+]
Morpholinos: bmp4 MO1 chrd.1 MO1 chrd.1 MO2 lrp6 MO1 rspo2 MO2 rspo2 MO3 znrf3 MO2

Disease Ontology terms: cancer
Phenotypes: Xla Wt + DN-bmpr1a (Fig. S 6 c d ) [+]

Article Images: [+] show captions
References [+] :
Antebi, Combinatorial Signal Perception in the BMP Pathway. 2017, Pubmed