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XB-ART-57519
Nat Commun January 1, 2020; 11 (1): 5570.
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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 .


Abstract
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: bmp4 bmpr1a chrd.1 eea1 foxg1 lamp1 lrp6 myod1 rnf43 rspo2 szl ventx1.2 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