Question

Provide (in detail) the signaling cascade that is initiated through Wint binding to the Frizzled receptor in the canonical pathway and what is the biological consequence of this binding interaction?

Answer 1

“Wnt” signaling pathway is also known as β -catenin signaling pathway. It is related with developmental biology and in this “Wnt” is the signaling molecule. This pathway is important because it is a conserved pathway from fruit fly, (Drosophila) to humans.

A negative “Wnt” regulator, namely “Axin”, is present in the cytoplasm. Prostaglandin E present in Extra Cellular Matrix activates “Wnt”.

When “Wnt” is present, it causes translocation of “Axin”, and itself binds to "Frizzled (Fz)" receptor on the membrane. “Axin” is dephosphorylated and deactivated.

Binding of “Wnt” to “Fz”, activates “Dishevelled”, which further block UQ (ubiquitin) of beta-catenin. (Please note that UQ is responsible for degradation of most cellular proteins; here the protein is beta-catenin. Now, when UQ is removed degradation of protein, β -catenin will not occur). So, a lot of β -catenin is accumulated in the cytoplasm. So, β -catenin goes into nucleus and binds to TCF. As a result, a transcription factor named Groucho is released. This further elevates transcription, which result in formation of “Wnt” inspired protein. This is also known as canonical “Wnt” signaling pathway.

These proteins will not form in absence of Wnt.

These proteins are important in embryonic development, bone development and maintenance of homeostasis. It is important to note that, if these proteins are not formed, then diseases like cancer, osteoporosis, congenital malformations etc. can occur in humans.