R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/β-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular resp...

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Main Authors:	Binnerts, Minke E., Kim, Kyung-Ah, Bright, Jessica M., Patel, Sejal M., Tran, Karolyn, Zhou, Mei, Leung, John M., Liu, Yi, Lomas, Woodrow E., Dixon, Melissa, Hazell, Sophie A., Wagle, Marie, Nie, Wen-Sheng, Tomasevic, Nenad, Williams, Jason, Zhan, Xiaoming, Levy, Michael D., Funk, Walter D., Abo, Arie
Formato:	Artigo
Idioma:	Inglês
Publicado em:	National Academy of Sciences 2007
Assuntos:	Biological Sciences
Acesso em linha:	https://ncbi.nlm.nih.gov/pmc/articles/PMC1965484/ https://ncbi.nlm.nih.gov/pubmed/17804805 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.0702305104
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id	pubmed-1965484
record_format	dspace
spelling	pubmed-19654842007-09-14 R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6 Binnerts, Minke E. Kim, Kyung-Ah Bright, Jessica M. Patel, Sejal M. Tran, Karolyn Zhou, Mei Leung, John M. Liu, Yi Lomas, Woodrow E. Dixon, Melissa Hazell, Sophie A. Wagle, Marie Nie, Wen-Sheng Tomasevic, Nenad Williams, Jason Zhan, Xiaoming Levy, Michael D. Funk, Walter D. Abo, Arie Proc Natl Acad Sci U S A Biological Sciences The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/β-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway. National Academy of Sciences 2007-09-11 2007-09-05 /pmc/articles/PMC1965484/ /pubmed/17804805 http://dx.doi.org/10.1073/pnas.0702305104 Text en © 2007 by The National Academy of Sciences of the USA
institution	US NLM
collection	PubMed Central
language	Inglês
format	Artigo
topic	Biological Sciences
spellingShingle	Biological Sciences Binnerts, Minke E. Kim, Kyung-Ah Bright, Jessica M. Patel, Sejal M. Tran, Karolyn Zhou, Mei Leung, John M. Liu, Yi Lomas, Woodrow E. Dixon, Melissa Hazell, Sophie A. Wagle, Marie Nie, Wen-Sheng Tomasevic, Nenad Williams, Jason Zhan, Xiaoming Levy, Michael D. Funk, Walter D. Abo, Arie R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
description	The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/β-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.
author	Binnerts, Minke E. Kim, Kyung-Ah Bright, Jessica M. Patel, Sejal M. Tran, Karolyn Zhou, Mei Leung, John M. Liu, Yi Lomas, Woodrow E. Dixon, Melissa Hazell, Sophie A. Wagle, Marie Nie, Wen-Sheng Tomasevic, Nenad Williams, Jason Zhan, Xiaoming Levy, Michael D. Funk, Walter D. Abo, Arie
author_facet	Binnerts, Minke E. Kim, Kyung-Ah Bright, Jessica M. Patel, Sejal M. Tran, Karolyn Zhou, Mei Leung, John M. Liu, Yi Lomas, Woodrow E. Dixon, Melissa Hazell, Sophie A. Wagle, Marie Nie, Wen-Sheng Tomasevic, Nenad Williams, Jason Zhan, Xiaoming Levy, Michael D. Funk, Walter D. Abo, Arie
author_sort	Binnerts, Minke E.
title	R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
title_short	R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
title_full	R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
title_fullStr	R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
title_full_unstemmed	R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
title_sort	r-spondin1 regulates wnt signaling by inhibiting internalization of lrp6
publisher	National Academy of Sciences
publishDate	2007
url	https://ncbi.nlm.nih.gov/pmc/articles/PMC1965484/ https://ncbi.nlm.nih.gov/pubmed/17804805 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1073/pnas.0702305104
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R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6

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