Wnt pathway

Question 1

What receptors can Wnt signalling bind to?

Answer 1

• Derailed/RYK
• ROR
• Frizzled
• Arrow/LRP5/6
• FRL1/crypto

Question 2

Canonical wnt signalling in the absence of Wnt

Answer 2

-There’s low level of beta catenin as its being continuously degraded

Question 3

Canonical wnt signalling in the presence of wnt signalling

Answer 3

• Wnt binds to the Frizzle receptor
• This brings together the LRP 5/6 co-receptor
  - This complex disassembles the degradation protein complex and therefore beta catenin accumulates in the cell and translocate into the nucleus leading to transcriptional activity

Question 4

What does beta catenin work as?

Answer 4

-Beta catenin works as a co activator of transcription

Question 5

What does beta catenin do in the nucleus in the absence of Wnt?

Answer 5

-TCF is bound to regulatory sequence of the DNA and to another protein. This is the cofactor protein called Groucho which prevents transcription.

Question 6

What does beta catenin do in the nucleus in the presence of Wnt?

Answer 6

• When beta catenin accumulates, the cofactor Groucho is displaced
• A beta catenin molecule will bind to TCF which recruits other proteins forming a complex
• This complex induces transcription

Question 7

What pathways are included in non-canonical wnt signalling?

Answer 7

Includes PCP and Ca2+ pathway.

Question 8

PCP pathway steps

Answer 8

• Wnt binds to frizzled receptor, activating the dishevelled protein
• Downstream of dishevelled, the Rho GTPases is activated
• This leads to the activation of proteins ROCK and JNK which affect the dynamics of the cytoskeleton including planar cell polarity and cell motility

Question 9

Ca2+ pathway steps

Answer 9

• Wnt binds to frizzled receptor, activating the dishevelled protein
• Downstream of dishevelled, Ca2+ is released
• The ca2+ modulates many proteins that leads to effects on the cytoskeleton but also effect transcription

Question 10

What are wnt levels modulated by?

Answer 10

Wnt levels are modulated by secreted wnt antagonists

Question 11

What are the 3 main extracellular antagonists?

Answer 11

• Sfrps (secreted frizzled related protein)
• Dkk1 (Dickkopf1)
• Wif-1 (Wnt inhibitory factor)

Question 12

What does the Sfrps antagonist do?

Answer 12

• Have a similar structure to extracellular structure of Frizzled
• Its binds wnt and sequester it

Question 13

What does the Dkk1 antagonist do?

Answer 13

• Dkk1 binds to the co-receptor LRP5/6

- This prevents LRP5/6 being recruited by frizzled and wnt binds to it

Question 14

What does the Wif-1 antagonist do?

Answer 14

-Wif-1 can bind to wnt and sequester it preventing the activation of the frizzled receptor