Non-Canonical Wnt Signaling Pathways

There are 19 different Wnt proteins present in humans that can regulate genes through three different pathways.

In all three of these pathways, the signaling in the target cells is mediated via transmembrane receptors called Frizzled receptors - as well as coreceptors such as low-density lipoprotein related proteins, or LRPs.

The Wnt protein binds to these proteins to form a Wnt-Frizzled-coreceptor complex.

But at this point, the three pathways diverge.

The non-canonical Wnt pathways are both Beta-catenin independent.

The second Wnt pathway, known as the planar cell polarity pathway, is facilitated by the Rho or Rac family of GTPases.

With the help of disheveled protein, they modulate the activity of Rho and JNK which are both involved in the coordination of cell polarization and migration during embryo development.

Finally, in the Wnt-Calcium pathway, the interaction of the Wnt-Frizzled-coreceptor complex with the disheveled protein transmits the signal to phospholipase C which in turn leads to the release of intracellular calcium ions from the endoplasmic reticulum.

The correct balance of calcium levels in cells is critical and any mutations affecting the regulation of calcium le