دورية أكاديمية
أعرض في EDS

R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling.

التفاصيل البيبلوغرافية
العنوان: R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling.
المؤلفون: Dubey R; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, United States., van Kerkhof P; Department of Cell Biology and Oncode Institute, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands., Jordens I; Department of Cell Biology and Oncode Institute, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands., Malinauskas T; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Pusapati GV; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, United States., McKenna JK; Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Li D; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Carette JE; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States., Ho M; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Siebold C; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom., Maurice M; Department of Cell Biology and Oncode Institute, Centre for Molecular Medicine, University Medical Centre Utrecht, Utrecht, Netherlands., Lebensohn AM; Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Rohatgi R; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, United States.
المصدر: ELife [Elife] 2020 May 20; Vol. 9. Date of Electronic Publication: 2020 May 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Wnt Signaling Pathway*, Heparan Sulfate Proteoglycans/*metabolism , Intercellular Signaling Peptides and Proteins/*metabolism , Receptors, G-Protein-Coupled/*metabolism, Cells, Cultured ; Developmental Biology ; Heparan Sulfate Proteoglycans/genetics ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Ligands ; Organoids ; Receptors, G-Protein-Coupled/genetics ; Thrombospondins
مستخلص: R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 and 3 potentiate WNT/β-catenin signaling in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 and 6 (Lebensohn and Rohatgi, 2018). We now show that heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis and ligand engineering. Mutations in RSPO3 residues predicted to contact HSPGs impair its signaling capacity. Conversely, the HSPG-binding domains of RSPO3 can be entirely replaced with an antibody that recognizes heparan sulfate (HS) chains attached to multiple HSPGs without diminishing WNT-potentiating activity in cultured cells and intestinal organoids. A genome-wide screen for mediators of RSPO3 signaling in cells lacking LGRs 4, 5 and 6 failed to reveal other receptors. We conclude that HSPGs are RSPO co-receptors that potentiate WNT signaling in the presence and absence of LGRs.
Competing Interests: RD, Pv, IJ, TM, GP, JM, DL, JC, MH, CS, MM, AL, RR No competing interests declared
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معلومات مُعتمدة: AI141970 United States NH NIH HHS; R35 GM118082 United States GM NIGMS NIH HHS; 26752 United Kingdom CRUK_ Cancer Research UK; R21 HD101980 United States HD NICHD NIH HHS; R01 AI141970 United States AI NIAID NIH HHS; C20724/A14414 United Kingdom CRUK_ Cancer Research UK; C20724/A26752 United Kingdom CRUK_ Cancer Research UK; 647278 International ERC_ European Research Council; GM118082 United States NH NIH HHS
فهرسة مساهمة: Keywords: LGR; R-spondin; WNT; cell biology; development; developmental biology; heparan sulfate proteoglycans; human; single chain antibody
المشرفين على المادة: 0 (Heparan Sulfate Proteoglycans)
0 (Intercellular Signaling Peptides and Proteins)
0 (Ligands)
0 (RSPO3 protein, human)
0 (Receptors, G-Protein-Coupled)
0 (Rspo2 protein, human)
0 (Thrombospondins)
تواريخ الأحداث: Date Created: 20200521 Date Completed: 20210323 Latest Revision: 20240922
رمز التحديث: 20240922
مُعرف محوري في PubMed: PMC7239654
DOI: 10.7554/eLife.54469
PMID: 32432544
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.54469