R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling

By Kendra S. Carmon, X. Gong, Q. Lin, Anthony Thomas, Qingyun J. Liu. Proceedings of the National Academy of Sciences of the United States of America, 2011

874 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c832cd229ccabb847ffb15a52cd51232a7477e4e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Nusse
2. Hans Clevers
3. Alexander van Oudenaarden

In Molecular Biology

1. Hans Clevers
2. R. Nusse
3. S. Angers
4. Z. Steinhart
5. W. de Lau
6. W. Peng
7. P. Gros
8. Alexander van Oudenaarden

Citations in the corpus

• Wnt/β-catenin signaling and disease. (2012, positive): “that they do not utilize G proteins (Carmon et al., 2011; de Lau et al., 2011).”
• Targeting cancer stem cell pathways for cancer therapy (2020, background): “The leucine-rich repeat containing GPCR4 (LGR4, or GPR48), together with its family members LGR5/ 6, binds to R-spondins 1–4 and leads to Wnt3A potentiation, activating Wnt signaling in breast CSCs.(171,172) Increased levels of CD44v6 mRNA in human pancreatic CSCs, lung CSCs, and colon CSCs promote ”
• Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis (2013, positive): “A crucial component of this culture medium is the Wnt agonist RSPO1 (Kim et al , 2005; Blaydon et al , 2006), the recently reported ligand of Lgr5 and its homologues (Carmon et al , 2011; de Lau et al , 2011).”
• The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength (2014, positive): “In intact cells, this leads to increased phosphorylation of Lrp5/6 and stabilization of b -catenin but does not involve G-protein signaling (Carmon et al. 2011; de Lau et al. 2011).”
• Wnt signaling in development and tissue homeostasis (2018, background): “However, the precise role of LGR5 and its homologs LGR4/LGR6 remained controversial until the discovery that they function as receptors for four R-spondin secreted proteins, RSPO1-RSPO4 (Carmon et al., 2011; de Lau et al., 2011; Glinka et al., 2011).”
• Wnt/ b -Catenin Signaling, Disease, and Emerging Therapeutic Modalities (2017, background): “The Lgr proteins bind R-spondins through their N-terminal ectodomain and do not appear to utilize G-proteins (Carmon et al., 2011; de Lau et al., 2011).”
• Prospective derivation of a Living Organoid Biobank of colorectal cancer patients (2015, positive): “In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity.”
• Identification of multipotent luminal progenitor cells in human prostate organoid cultures (2014, background): “These cultures can be initiated from single Lgr5+ stem cells and are based on the addition of the Lgr4/5 ligand R-spondin1, a potent Wnt pathway agonist (Binnerts et al., 2007; Carmon et al., 2011; de Lau et al., 2011).”
• Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. (2013, background): “Of note, only Lgr5+ stem cells—and none of the other epithelial cell types— will grow out in a clonal fashion into secondary organoids in culture (Sato et al., 2009, 2011).”
• The intestinal crypt, a prototype stem cell compartment. (2013, background): “Alternatively, rare oncogenic point mutants can occur in b-catenin (Morin et al., 1997), and gene fusions involving Tcf4/Tcf7l2 (Bass et al., 2011) and the secreted Wnt agonists called Rspondins (Seshagiri et al., 2012) have very recently been observed in colon cancer.”