What is the Difference Between Canonical and Noncanonical WNT Pathway

The key difference between canonical and noncanonical WNT pathway is that canonical WNT pathway is a type of WNT signalling pathway that activates target genes through β-catenin activation, while noncanonical WNT pathway is a type of WNT signalling pathway that activates target genes without activation of the β-catenin.

The WNT signalling pathway is a signal transduction pathway. It begins with proteins that pass signals into a cell through the cell surface receptors. This pathway usually uses paracrine and autocrine cell communication. There are two main WNT signalling pathways: canonical and noncanonical WNT pathways.

CONTENTS

1. Overview and Key Difference
2. What is Canonical WNT Pathway
3. What is Noncanonical WNT Pathway
4. Similarities – Canonical and Noncanonical WNT Pathway
5. Canonical vs Noncanonical WNT Pathway in Tabular Form
6. Summary – Canonical vs Noncanonical WNT Pathway

What is Canonical WNT Pathway?

Canonical WNT pathway is a type of WNT signalling pathway. It uses β-catenin to activate target genes. This pathway is also known as Wnt/β-catenin pathway. This pathway causes an accumulation of β-catenin in the cytoplasm. After the accumulation, β-catenin is eventually translocated into the nucleus to act as a transcriptional coactivator of transcription factors that normally belong to the TCF/LEF family. This allows β-catenin to subsequently induce a cellular response via gene transduction alongside the transcription factors of the TCF/LEF family. Moreover, β-catenin also recruits other transcriptional coactivators such as BCL9, pygopus, and parafibromin/hyrax while inducing the cellular response.

Furthermore, without the WNT protein, β-catenin would not accumulate in the cytoplasm as usual. This is because a destruction complex can degrade β-catenin without the WNT protein. This destruction complex includes proteins such as axin, adenomatosis polyposis coli (APC), protein phosphatase 2A (PP2A), glycogen synthase kinase 3 (GSK3), and casein kinase 1α (CK1α). The above destruction complex degrades β-catenin by targeting it for ubiquitination and sending it to digest by the proteasome. However, when the WNT protein binds with other factors like Fz and LRP5/6, the function of the above destruction complex becomes disrupted.

What is Noncanonical WNT Pathway?

The noncanonical WNT pathway is a type of WNT signalling pathway that activates target genes without recruiting the β-catenin. The noncanonical WNT pathway does not use β-catenin and co-receptors such as LRP-5/6. Instead, it uses co-receptors such as NRH1, Ryk, PTK7, or ROR2. For example, the noncanonical planar cell polarity (PCP) pathway is a type of noncanonical WNT pathway.

PCP pathway is activated through the binding of WNT protein to Fz factor and its co-receptor. The receptor then recruits Dsh. Dsh uses its domains to form a complex with DAAM1. Later, Daam1 activates the small G-protein Rho via a guanine exchange factor. Ultimately, Rho activates the ROCK, one of the main regulators of the cytoskeleton. Furthermore, Dsh also forms a complex with rac1 and mediates profilin binding to actin. Rac1 activates JNK, which can lead to actin polymerization, while profilin binding to actin can lead to the restructuring of the cytoskeleton and gastrulation.

What are the Similarities Between Canonical and Noncanonical WNT Pathway?

• Canonical and noncanonical WNT pathways are the two main pathways of the WNT signalling pathway.
• Both these pathways are successful in target gene expression.
• WNT protein and co-receptor play pivotal roles in both pathways.
• Abnormal expression of both pathways leads to various diseases.

What is the Difference Between Canonical and Noncanonical WNT Pathway?

Canonical WNT pathway is a type of WNT signalling pathway that activates target genes through β-catenin activation, while noncanonical WNT pathway is a type of WNT signalling pathway that activates target genes without activation of the β-catenin. Thus, this is the key difference between canonical and noncanonical WNT pathway. Furthermore, the co-receptor of the canonical WNT pathway is LRP5/6, while the co-receptor of noncanonical WNT pathway is NRH1, Ryk, PTK7, or ROR2.

The below infographic presents the differences between canonical and noncanonical WNT pathway in tabular form for side by side comparison.

Summary – Canonical vs Noncanonical WNT Pathway

Canonical and noncanonical WNT pathways are different types of pathways of the WNT signalling pathway. In both these pathways, WNT protein plays a central role and ultimately induces target genes. However, canonical WNT pathway is a type of WNT signalling pathway that activates target genes through β-catenin activation, while noncanonical WNT pathway is a type of WNT signalling pathway that activates target genes without activation of the β-catenin. So, this summarizes the difference between canonical and noncanonical WNT pathway.

Reference:

1. “What Is Canonical Wnt Receptor Signaling Pathway?” MBInfo.
2. Ackers, Ian, and Ramiro Malgor. “Interrelationship of Canonical and Noncanonical Wnt Signalling Pathways in Chronic Metabolic Diseases.” Diabetes & Vascular Disease Research, U.S. National Library of Medicine.

Image Courtesy:

1. “Canonical Wnt pathway with Wnt.” By Gpruett2 – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Noncanonical Wnt calcium pathway” By Gpruett2 – Own work (CC BY-SA 3.0) via Commons Wikimedia