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Literature DB >> 23756651

The structural basis of R-spondin recognition by LGR5 and RNF43.

Po-Han Chen¹, Xiaoyan Chen, Zhenghong Lin, Deyu Fang, Xiaolin He.

Abstract

R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-protein-coupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1-RNF43 interface, which promises therapeutic targeting.

Entities: Chemical Disease Gene Species

Keywords: E3 ubiquitin ligase; LGR5; R-spondin; RNF43; Wnt signaling; furin-like repeat

Mesh：

Substances：

Year: 2013 PMID： 23756651 PMCID： PMC3701190 DOI： 10.1101/gad.219915.113

Source DB: PubMed Journal: Genes Dev ISSN： 0890-9369 Impact factor: 11.361

36 in total

Review 1. The R-spondin protein family.

Authors: Wim B M de Lau; Berend Snel; Hans C Clevers
Journal: Genome Biol Date: 2012 Impact factor: 13.583

Review 2. Wnt/β-catenin signaling and disease.

Authors: Hans Clevers; Roel Nusse
Journal: Cell Date: 2012-06-08 Impact factor: 41.582

3. Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.

Authors: Wim de Lau; Nick Barker; Teck Y Low; Bon-Kyoung Koo; Vivian S W Li; Hans Teunissen; Pekka Kujala; Andrea Haegebarth; Peter J Peters; Marc van de Wetering; Daniel E Stange; Johan E van Es; Daniele Guardavaccaro; Richard B M Schasfoort; Yasuaki Mohri; Katsuhiko Nishimori; Shabaz Mohammed; Albert J R Heck; Hans Clevers
Journal: Nature Date: 2011-07-04 Impact factor: 49.962

4. Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

Authors: Nick Barker; Maarten B Rookmaaker; Pekka Kujala; Annie Ng; Marc Leushacke; Hugo Snippert; Marc van de Wetering; Shawna Tan; Johan H Van Es; Meritxell Huch; Richard Poulsom; Marianne C Verhaar; Peter J Peters; Hans Clevers
Journal: Cell Rep Date: 2012-09-20 Impact factor: 9.423

Review 5. The complex world of WNT receptor signalling.

Authors: Christof Niehrs
Journal: Nat Rev Mol Cell Biol Date: 2012-11-15 Impact factor: 94.444

6. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor.

Authors: Xuliang Jiang; Heli Liu; Xiaoyan Chen; Po-Han Chen; David Fischer; Venkataraman Sriraman; Henry N Yu; Steve Arkinstall; Xiaolin He
Journal: Proc Natl Acad Sci U S A Date: 2012-07-16 Impact factor: 11.205

7. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors.

Authors: Bon-Kyoung Koo; Maureen Spit; Ingrid Jordens; Teck Y Low; Daniel E Stange; Marc van de Wetering; Johan H van Es; Shabaz Mohammed; Albert J R Heck; Madelon M Maurice; Hans Clevers
Journal: Nature Date: 2012-08-30 Impact factor: 49.962

8. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner.

Authors: Huai-Xiang Hao; Yang Xie; Yue Zhang; Olga Charlat; Emma Oster; Monika Avello; Hong Lei; Craig Mickanin; Dong Liu; Heinz Ruffner; Xiaohong Mao; Qicheng Ma; Raffaella Zamponi; Tewis Bouwmeester; Peter M Finan; Marc W Kirschner; Jeffery A Porter; Fabrizio C Serluca; Feng Cong
Journal: Nature Date: 2012-04-29 Impact factor: 49.962

9. Structural basis of Wnt recognition by Frizzled.

Authors: Claudia Y Janda; Deepa Waghray; Aron M Levin; Christoph Thomas; K Christopher Garcia
Journal: Science Date: 2012-05-31 Impact factor: 47.728

10. R-Spondin potentiates Wnt/β-catenin signaling through orphan receptors LGR4 and LGR5.

Authors: Heinz Ruffner; Joëlle Sprunger; Olga Charlat; Juliet Leighton-Davies; Bianka Grosshans; Adrian Salathe; Svenja Zietzling; Valérie Beck; Maxime Therier; Andrea Isken; Yang Xie; Yue Zhang; Huaixiang Hao; Xiaoying Shi; Dong Liu; Qinhui Song; Ieuan Clay; Gabriele Hintzen; Jan Tchorz; Laure C Bouchez; Gregory Michaud; Peter Finan; Vic E Myer; Tewis Bouwmeester; Jeff Porter; Marc Hild; Fred Bassilana; Christian N Parker; Feng Cong
Journal: PLoS One Date: 2012-07-16 Impact factor: 3.240

55 in total

Review 1. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration.

Authors: Nick Barker
Journal: Nat Rev Mol Cell Biol Date: 2013-12-11 Impact factor: 94.444

2. Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R-spondin.

Authors: Yang Xie; Raffaella Zamponi; Olga Charlat; Melissa Ramones; Susanne Swalley; Xiaomo Jiang; Daniel Rivera; William Tschantz; Bo Lu; Lisa Quinn; Chris Dimitri; Jefferson Parker; Doug Jeffery; Sheri K Wilcox; Mike Watrobka; Peter LeMotte; Brian Granda; Jeffrey A Porter; Vic E Myer; Andreas Loew; Feng Cong
Journal: EMBO Rep Date: 2013-10-29 Impact factor: 8.807

3. Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

Authors: Jin-Gen Xu; Chunfeng Huang; Zhengfeng Yang; Mengmeng Jin; Panhan Fu; Ni Zhang; Jian Luo; Dali Li; Mingyao Liu; Yan Zhou; Yongqun Zhu
Journal: J Biol Chem Date: 2014-12-05 Impact factor: 5.157

Review 10. Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms.

Authors: Laura Novellasdemunt; Pedro Antas; Vivian S W Li
Journal: Am J Physiol Cell Physiol Date: 2015-08-19 Impact factor: 4.249