Wnt-Frizzled-LRP5/6 complex

Definition

Target type: cellularcomponent

A protein complex containing a secreted Wnt protein associated with its receptor, Frizzled (Fz), and co-receptor low density lipoprotein receptor-related protein 5 (LRP5) or LRP6. [GOC:bf, GOC:PARL, PMID:11448771, PMID:20093360]

The Wnt-Frizzled-LRP5/6 complex is a multiprotein assembly that plays a crucial role in Wnt signaling, a critical pathway involved in embryonic development, tissue homeostasis, and disease. This complex forms at the plasma membrane of cells and consists of several key components:

1. **Wnt proteins:** These secreted glycoproteins act as ligands for the Frizzled receptors. They bind to Frizzled and LRP5/6, initiating the signaling cascade.

2. **Frizzled (Fzd) receptors:** These transmembrane proteins belong to the seven-transmembrane receptor family. They possess an extracellular cysteine-rich domain that binds Wnt proteins and an intracellular C-terminal tail that interacts with Dishevelled (Dvl) upon Wnt activation.

3. **Low-density lipoprotein receptor-related protein 5/6 (LRP5/6):** These transmembrane proteins act as coreceptors for Wnt signaling. They contain extracellular domains that bind Wnt proteins and intracellular domains that interact with Axin and the scaffolding protein Dishevelled (Dvl).

4. **Dishevelled (Dvl):** This cytoplasmic protein acts as a scaffold for downstream signaling molecules. It binds to the intracellular domains of Frizzled and LRP5/6, bringing them together to form the signaling complex.

5. **Axin:** This scaffolding protein acts as a negative regulator of the Wnt pathway. It interacts with LRP5/6 and the downstream signaling component GSK-3β, promoting the degradation of β-catenin.

6. **Glycogen synthase kinase 3β (GSK-3β):** This kinase phosphorylates β-catenin, targeting it for degradation. However, in the presence of Wnt signaling, the complex sequesters GSK-3β, preventing β-catenin phosphorylation and degradation.

7. **β-catenin:** This cytoplasmic protein is the main effector molecule of the Wnt pathway. In the absence of Wnt signaling, β-catenin is targeted for degradation. However, when Wnt binds to the complex, β-catenin accumulates in the cytoplasm and translocates to the nucleus, where it activates the transcription of Wnt target genes.

The assembly of the Wnt-Frizzled-LRP5/6 complex at the plasma membrane allows for efficient signal transduction. The interaction between Wnt, Frizzled, and LRP5/6 initiates a cascade of events that ultimately leads to the stabilization and nuclear accumulation of β-catenin. This complex is crucial for regulating cellular processes such as cell proliferation, differentiation, and migration.'
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Proteins (1)

Compounds (3)