A finger on the pulse of Wnt receptor signaling.
In a recent issue of Nature, Hao et al. report an unexpected link between the secreted stem cell factor/Wnt agonist R-spondin and Wnt receptors through the transmembrane ZNRF3 protein, a RING finger ubiquitin ligase. ZNRF3 acts to turn over Frizzled and LRP6 receptors. R-spondin binds to ZNRF3, in addition to transmembrane LGR4/5 receptors, to antagonize degradation of the Wnt receptors by ZNRF3, thereby resulting in increased Frizzled and LRP6 levels and a greater Wnt response.
The F. M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Bryan T
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D051157:Frizzled Receptors / Q000378:metabolism; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D060490:Receptors, Wnt / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000819:agonists / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000098907:R-Spondins
D051157:Frizzled Receptors; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D060490:Receptors, Wnt; D019089:Stem Cell Factor; D019699:Thrombospondins; D044767:Ubiquitin-Protein Ligases; D051153:Wnt Proteins; C555475:LRP6 protein, human; C503243:RSPO1 protein, human; D000098907:R-Spondins; C572950:ZNRF3 protein, human