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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Related Experiment Video

Updated: Oct 21, 2025

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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LRPs in WNT Signalling.

Gary Davidson1

  • 1Institute of Biological and Chemical Systems-Functional Molecular Systems (IBSC-FMS), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany. gary.davidson@kit.edu.

Handbook of Experimental Pharmacology
|September 7, 2021
PubMed
Summary
This summary is machine-generated.

The WNT/β-catenin pathway is crucial for development and homeostasis. Low-density-lipoprotein-receptor-related proteins (LRP5/6) act as essential co-receptors, mediating WNT signal transduction and offering therapeutic targets for diseases.

Keywords:
DKK therapeutic antibodiesLRPLRP4LRP5LRP5 disease mutationsLRP6LRP6 disease mutationsLRP6 structureSclerostin therapeutic antibodiesWntWnt co-receptorWnt surrogates

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The WNT/β-catenin signalling pathway regulates cell communication, development, and homeostasis.
  • Deregulation of this pathway is linked to various human diseases, driving pharmaceutical interest.
  • Low-density-lipoprotein-receptor-related proteins (LRP5/6) are critical co-receptors for WNT signal transduction with Frizzled (FZD) receptors.

Purpose of the Study:

  • To provide a historical overview of research on LRPs in WNT/β-catenin signalling over the past 20 years.
  • To detail the structural, functional, and mechanistic aspects of LRP biology.
  • To explore the implications of LRP biology for targeting the WNT pathway therapeutically.

Main Methods:

  • Literature review and historical analysis of WNT/β-catenin signalling research.
  • Focus on the role of LRP5/6 as WNT co-receptors.
  • Examination of LRP structural and functional characteristics.

Main Results:

  • LRP5/6 are essential co-receptors for WNT/β-catenin signalling, interacting with diverse WNT and FZD subtypes.
  • LRP5/6 possess complex extracellular domains that bind WNTs and WNT inhibitors.
  • Significant progress has been made in understanding LRPs' central role in WNT signalling over two decades.

Conclusions:

  • LRP5/6 are indispensable components of the WNT/β-catenin pathway.
  • Understanding LRP structure-function relationships is key to developing targeted therapies.
  • The WNT pathway, particularly LRP involvement, presents both challenges and opportunities for drug development.