WNT Signalling

Question 1

4 Steps for a Rapid Response in Gene Expression Due to an Environmental Stimulus

Answer 1

1) surface to recognize change
2) existing proteins networks
3) mechanism enter nucleus
4) poised genes

Question 2

2 Pathways of WNT signalling

Answer 2

Canonical = change in gene expression
Non-canonical

Question 3

Common Parts of WNT Pathway

Answer 3

• WNT ligand (19 in total)
• Frizzled Receptor

Question 4

Inactive State WNT Signalling

Answer 4

WNT ligand no interact with FZD receptor
- FZD receptor ubiquitinated = degrade
- Disheveled ubiquitinated = degrade
- β-catenin (phosphorylated) + destruction complex = degrade by proteasome
- TCF bound to genes –> not activated

Question 5

Active State WNT Signalling

Answer 5

RSPO binds to surface = no ubiquitination of FZD
WNT ligand binds to FZD
- Disheveled binds to FZD = deactivate β-catenin destruction complex
- β-catenin translocate to nucleus, bind to TCF = activate

Question 6

Canonical WNT Signalling - Mutations

Answer 6

delete β-catenin or WNT3 = early embryonic lethality
β-catenin mutations
- intellectual disability
- microcephaly
- ALSO – affects adherens junctions

Question 7

Non-Canonical WNT Signalling Pathways (2)

Answer 7

Planar Cell Polarity
- WNT11 ligand
- MAPK and Jun phosphorylation

WNT/Calcium
- WNT5 ligand
- PLC/PKC and NFAT phosphorylation

Question 8

Non-Canonical WNT Signalling - Mutations

Answer 8

loss WNT5 = short limbs
increase WNT5 = abnormal skull development
dosage important!

Question 9

WNTs in Cancer

Answer 9

• high levels WNT signalling = proliferation
• less WNT signalling as migrate up gland

somatic mutations to pathway
- WNT ligand = osteocarcinoma
- destruction complex = adrenal cancer
- APC (in complex) = colorectal cancer
- TCF = liver + colorectal cancer