Wnt System

The Wnt system

Figure 1. A simplified representation of the Wnt signalling
pathways.  

The Wnt system is a signal transduction signalling pathway in metazoan animals. This means it involves the transfer of an extra-cellular signal to a cell surface receptor and into the cell. The system is important in altering cell migration, cell polarity, neural patterning and organogenesis during embryonic development. (K.Yuko, R.Habas. 2008) 

Wnt morphogens are secreted glycoproteins that activate cell-surface Frizzled (Fz) receptors. Fz receptors have 7 trans-membrane helices including a cysteine-rich domain (CRD) that binds Wnt proteins.

Regulations of the system can be controlled by Wnt antagonists present in the extracellular space, including the Wnt inhibitory factor 'WIF'.
There are two overall classes of antagonists, one that bind Wnt morphogens and the other that bind to the Wnt receptor. (K. Yoshiaki, R. Kypta 2003)

Once the signal has activated the Fz receptor, it passes to a phosphoprotein called Dishevelled (Dsh) in the cytoplasm. The journey of the signal following this step is where the Wnt system splits into three unique pathways; the canonical pathway, the non-canonical planar cell polarity pathway, and the non-canonical Wnt/calcium pathway.

Figure 2. A simplified diagram of the Wnt
β-catenin pathway. Activation of Fz and the LPR
receptors leads to a build up of β-catenin and
activation of transcription.

Canonical Pathway
This pathway is also known as the Wnt / β-catenin pathway. In this pathway the signal is transferred by the Wnt protein, causing an accumulation of β-catenin in the cytoplasm due to deactivation of the 'destruction complex'. In the absence of Wnt signalling, the 'destruction complex' tags β-catenin with ubiquitin, targeting it to the proteosome. (Aberle et al. 1997). With the Wnt signal, β-catenin can act as a transcription factor. This pathway requires co-receptors LDL-related proteins 5 and 6. (LRP5/6). (He et al. 2004)
In addition, there are other possible receptors used. These include Ryk and Ror2.

Non-canonical Pathway

This pathway is also known as the β-catenin independent pathway.

There are two individual non-canonical pathways, the planar cell polarity and calcium pathways. 
The planar cell polarity pathway leads to actin modification. The calcium pathway regulates release of calcium from the endoplasmic reticulum.

This video shows the activation of the Wnt canonical pathway in normal and cancerous cells. 

Aberle, H. et al., 1997. beta-catenin is a target for the ubiquitin-proteasome pathway. The EMBO journal, 16(13), pp.3797–804. [Accessed November 12, 2013].

He, X. et al., 2004. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development (Cambridge, England), 131(8), pp.1663–77. A [Accessed November 18, 2013].

Kawano, Y. & Kypta, R., 2003. Secreted antagonists of the Wnt signalling pathway. Journal of cell science, 116(Pt 13), pp.2627–34. [Accessed December 13, 2013].

Komiya, Y. & Habas, R., 2008. Wnt signal transduction pathways. Organogenesis, 4(2), pp.68–75. [Accessed December 13, 2013].