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Wnt Ligands & Receptors Proteins

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Wnt Ligands & Receptors Proteins

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Wnt Ligands & Receptors Proteins Background

The Wnt signaling pathway is a set of multiple downstream channels that is triggered by the binding of the ligand protein Wnt to membrane protein receptors. Through this pathway, extracellular signals are transmitted into the cell through the activation process of the intracellular segment of the cell surface receptor. Wnt is an acronym for genetics and stands for "Wingless/Integrated". The Wnt signaling pathway presents two types of signaling between cells: intercellular communication (paracrine) or autologous cell communication (autocrine). Wnt signaling pathways are highly genetically conserved among animals and are very similar among different animal species. In 1982, the Wnt gene was first discovered in mouse breast cancer. Because this gene activation was dependent on the insertion of mouse breast cancer-associated virus genes, it was then named the Int1 gene. Subsequent studies have shown that the Int1 gene plays an important role in normal mouse embryonic development, and similar to the function of the fruit fly's Wingless gene, it can control the axial development of the embryo. Subsequent studies have suggested the importance of the Int1 gene in embryonic development of the nervous system. Because of the similarity of gene and protein functions between the two, the researchers merged Wingless and Int1 and named it Wnt gene. The human Wnt gene is located at 12q13. In embryonic development, the important signaling systems regulated by Wnt genes are collectively referred to as the Wnt pathway.

Channel composition member

Wnt protein (Wnt ligand), Wnt receptor (Frizzled family protein and LDL receptor related protein (LRP)), Dishevelled (Dsh/Dvl) protein, β-catenin), Glycogen synthase kinase 3β (GSK-3β), Axin/Conductin, APC (adenomatous polyposis coli) protein.

Wnt Ligands & Receptors Proteins Figure 1. Crystal protein structure of Wnt8 and the cysteine-rich domain of Frizzled 8.

Wnt/β-catenin pathway

Wnt is a type of secreted glycoprotein that works through autocrine or paracrine. The Wnt signaling pathway can cause the accumulation of intracellular β-catenin. Β-catenin (called Armadillo protein in Drosophila) is a multifunctional protein. It interacts with cadherin at the junction of cells and participated in the formation of adhesive tape, and free β-catenin can enter the nucleus and regulate gene expression. Wnt signaling plays an important role in animal development, and its abnormal expression or activation can cause tumors. The Wnt signal pathway can be summarized as: Wnt→Frz→Dsh→degradation complex of β-catenin dissolves → β-catenin accumulates, enters the nucleus→ TCF/LEF→ gene transcription (such as c-myc, cyclinD1). The researchers found that the Wnt protein family needs a complex: RetromerComplex. When this circulating system is broken in the cell, Wnt signaling proteins cannot be delivered. A transport receptor called Wntless (Wls) is blocked, and Gradual degradation.

Wnt Ligands & Receptors Proteins Figure 2. Canonical Wnt pathway.

Functions

Wnt signals are involved in brain formation. Wnt 3a knockout mouse embryos have impaired hippocampal development; Lef homozygous mutations can cause mouse embryos to lack all of the hippocampal gyrus. Wnt/LEF/TCF genes work together to participate in the development of the hippocampal gyrus of the brain.The Wnt signal is involved in the reconstruction of the growth cone and the formation of multisynaptic spheroids (when mossy nerve fibers are in contact with granular cells). Involved in the initial process of axon formation: Wnt7a can induce the axon and growth cone reconstruction of mossy nerve fibers and the assembly of hapin I.

Wnt signaling is involved in limb initiation and apical ectodermal ridge formation in vertebrates. Three Wnt signaling molecules (Wnt2b, Wnt3a, Wnt8c) are the key inducers of signal transduction; the information exchange between FGF and Wnt signals is also related to the formation of the inner ear.

Wnt signaling and tumorigenesis. Early evidence that Wnt signaling is involved in tumor formation is derived from the oncogene Int1 isolated from mouse breast cancer and activated by viral insertion (see Overview). In addition, activation mutations in the Wnt pathway are the major genetic alterations in early premalignant lesions of the small intestine, including abnormal crypt foci and small polyps.

Signal pathways that regulate EMT. Brief introduction of the signal pathway network involved in regulating EMT process: Wnt signaling pathway can inhibit phosphorylation mediated by glycogen synthase kinase -3β (GSK3β) and inhibit β-catenin (β-catenin) in cytoplasm. catenin) to induce EMT conversion. Β-catenin, which has a large increase in intracellular abundance, will be transferred into the nucleus, and as a transcription factor subunit induces the expression of a large number of genes. Many of the expression products of these target genes are transcription factors that can induce the EMT conversion process.

Reference:

  1. Nusse R, et al.; A new nomenclature for int-1 and related genes: the Wnt gene family. Cell. 1991, 64 (2): 231.

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