User talk:Z3439257

Wnt calcium ion signalling pathway

General introduction

• Ligands: Wnt-4, -5a & -11
• Downstream targets: CAMKII, calcineurin & PKC
• Main functions:
  • Regulation of cell adhesion, migration and tissue separation (mediated by CAMKII)
  • Inhibition of TCF/Beta-catenin signalling (mediated by calcineurin)
  • Ventral patterning (mediated by PKC)

Molecular Basis

1. Wnt-4, -5a & -11 are ligands identified to be able to activate wnt/calcium signalling pathway. wnt ligands binds to Fz receptors( more)

2.

were identified as ligands specifically activate this pathway. Wnt (5a) interact with Fz receptor. Fz receptor functions as a G-protein coupled receptor which activates Gaq/11. Gaq/11 further cleaves PIP2 into DAG and IP3. IP3 then interacts with the IP3R on the surface of endoplasmic reticulum and causes increase in intracellular calcium ions. Those calcium ions will then react with CAMKII or calcineurin leading to further internal effects. DAG and calcium ions are also able to activate proteins belongs to PKC family which also posses various cellular effects.

PMCID: PMC4342031 CAMKII physically interacts with DSH2. It is DSH2 which activates calcium ion pathway but not DSH1.

Embryological events based on animal models

Xenopus

1. Gastrulation

PMID 11677610 Signalling through Fz7 receptor is required to prevent fusion of blastocoel roof (BCR) and the mesoderm, even though there is not physical barrier between those two cell populations and those two cell types are expressing the same cadherin. This separation is essential for proper involution and further movement of the mesoderm.

Moreover, this Fz7 activation is also involved in separation of mesoderm cells and therefore, contributes to the anterior mesoderm differentiation. Mesodermal cells with Fz7 activation remains separated with the endodermal BCR while some cells tend to sink down to the BCR and fuse with the cells there.

This separation was proved to be achieved through activation of PKC alpha downstream of wnt-11/ Fz7 signalling.

• Convergent extension (CE) movement in xenopus and vertebrae.

PMID 12729560 In xenopus explants, wnt-11 are expected to interact with Fz 7 and activates wnt/calcium signalling pathway.

PMID 24489854 In xenopus and other vertebrates, wnt ligands firstly activate Fz 7 receptor protein on the surface of cell membrane which couples a G-protein at its intramembraneous portion. The beta & gamma-subunits of the G-protein bind with beta-arrestin 2 (Arrb2) and Dishevelled (Dvl) proteins to form a functional complex. CAMKII and PKC alpha were reported to be two downstream targets activated by this complex in xenopus explants. Moreover, Arrb2 was also reported to be required for activation and translocation of PKC alpha in xenopus. The consequence of this signalling pathway is the migration of cells. Convergent extension (CE) movements of the dorsal mesoderm were further researched in the same literature and were expected to be regulated by wnt/calcium ion signalling pathway.

Glossary

convergent extension