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Canonical Wnt Signaling Pathway02:54

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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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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...
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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Wnt acylation and its functional implication in Wnt signalling regulation.

Claudia Y Janda1, K Christopher Garcia1

  • 1*Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, U.S.A.

Biochemical Society Transactions
|April 8, 2015
PubMed
Summary

Wnt proteins, crucial for development, require palmitoylation for secretion and function. This fatty acylation enables unique receptor binding, highlighting its essential role in Wnt signaling pathways.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Wnt proteins are vital signaling molecules regulating embryogenesis and tissue homeostasis.
  • Palmitoylation, a post-translational modification, is essential for Wnt secretion and biological function.
  • Wnt signaling pathways are critical for numerous cellular processes.

Purpose of the Study:

  • To review the current understanding of Wnt protein acylation.
  • To elucidate the functional role of Wnt acylation in regulating Wnt signaling.
  • To highlight the unique receptor-ligand interactions mediated by Wnt fatty acylation.

Main Methods:

  • Review of existing literature on Wnt protein modification and signaling.
  • Analysis of structural data, including the XWnt8-Fzd8-CRD complex.
  • Integration of evidence on Wnt interactions with receptors and modulators.

Main Results:

  • Palmitoylation is a key post-translational modification for Wnt secretion and function.
  • Fatty acids act as critical contact residues in Wnt receptor engagement.
  • Structural studies reveal unique Wnt-receptor recognition mechanisms involving fatty acids.
  • Wnts utilize fatty acids to interact with signaling modulators and alternative receptors.

Conclusions:

  • Wnt acylation is fundamental to Wnt protein secretion, function, and receptor interactions.
  • The fatty acid modification provides a unique mechanism for Wnt signaling pathway regulation.
  • Understanding Wnt acylation is crucial for deciphering complex developmental and homeostatic processes.