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Angiopoietin-like 4 Is a Wnt Signaling Antagonist that Promotes LRP6 Turnover
Deutsch Krebsforschungszentrum DKFZ, Germany.
Deutsch Krebsforschungszentrum DKFZ, Germany.
Deutsch Krebsforschungszentrum DKFZ, Germany.
Deutsch Krebsforschungszentrum DKFZ, Germany.
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2017 (English)In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 43, no 1, 71-+ p.Article in journal (Refereed) Published
Abstract [en]

Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation ofWnt/b-catenin signaling. Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a Wnt antagonist to promote notochord formation and prevent muscle differentiation. This unexpected function ofANGPTL4 invites reinterpretation of its diverse physiological effects in light of Wnt signaling and may open therapeutic avenues for human disease.

Place, publisher, year, edition, pages
CELL PRESS , 2017. Vol. 43, no 1, 71-+ p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-142148DOI: 10.1016/j.devcel.2017.09.011ISI: 000412557400009PubMedID: 29017031OAI: oai:DiVA.org:liu-142148DiVA: diva2:1151418
Note

Funding Agencies|DFG [SFB 873]; HHMI

Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2017-11-06

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CiteExportLink to record
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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
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  • Other style
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Language
  • de-DE
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