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Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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 results in tumor...

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Related Experiment Video

Updated: May 29, 2026

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
08:10

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients

Published on: December 14, 2015

Dissecting molecular differences between Wnt coreceptors LRP5 and LRP6.

Bryan T MacDonald1, Mikhail V Semenov, He Huang

  • 1F. M. Kirby Neurobiology Center, Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

Plos One
|September 3, 2011
PubMed
Summary

Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) are crucial for Wnt signaling. A specific region in LRP6 enhances its signaling activity compared to LRP5, offering new therapeutic targets.

More Related Videos

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Related Experiment Videos

Last Updated: May 29, 2026

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
08:10

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients

Published on: December 14, 2015

Modeling Paracrine Noncanonical Wnt Signaling In Vitro
11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) are Wnt co-receptors vital for the canonical β-catenin pathway.
  • Both LRP5 and LRP6 are implicated in skeletal remodeling, osteoporosis, and cancer, making them significant therapeutic targets.
  • While LRP6 generally shows higher Wnt signaling efficacy than LRP5, the underlying molecular mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the molecular basis for the differential Wnt signaling activity between LRP5 and LRP6.
  • To identify specific regions within the cytoplasmic domains of LRP5 and LRP6 that contribute to their distinct signaling capabilities.
  • To investigate the role of phosphorylation and Axin binding in the differential signaling of LRP5 and LRP6.

Main Methods:

  • Generation of chimeric receptors by swapping cytoplasmic domains of LRP5 and LRP6 (LRP5C and LRP6C).
  • Biochemical and functional assays to assess Wnt signaling activity of chimeric receptors.
  • In vitro phosphorylation assays to evaluate Axin-binding capabilities.

Main Results:

  • Chimeric LRP6 cytoplasmic domain (LRP6C) exhibited significantly higher Wnt signaling activity than LRP5C.
  • In vitro, both LRP5C and LRP6C showed similar Axin-binding capacity after phosphorylation, suggesting differences arise before Axin binding.
  • A specific "gap4" region between the two most carboxyl PPPSPxS motifs in LRP6 was identified as critical for its enhanced signaling.
  • Modifications in the LRP5 "gap4" region increased LRP5 phosphorylation and signaling to levels comparable to LRP6.
  • Evidence suggests direct binding of phosphorylated LRP5/LRP6 to Axin, independent of GSK3 kinase.

Conclusions:

  • A novel molecular mechanism regulating differential LRP5 and LRP6 phosphorylation and signaling activity has been uncovered.
  • The "gap4" region in the cytoplasmic tail plays a key role in modulating LRP5/LRP6 Wnt signaling efficacy.
  • These findings provide critical insights into the distinct roles of LRP5 and LRP6 in Wnt signaling and offer potential avenues for targeted therapeutic interventions.