L13- Wnt signalling

Question 1

What is autocrine signalling?

Answer 1

Signals a cell gives to itself

Question 2

What is paracrine signalling?

Answer 2

Signals a cell gives to neighbouring cells e.g local mediators, membrane bound signals and neurotransmitters

Question 3

What is endocrine signalling?

Answer 3

Signals a cell gives to cells in different locations e.g hormones

Question 4

What is the cell signalling cascade?

Answer 4

Extracellular signal molecule
Receptor protein
Intracellular signalling proteins
Effector proteins
Response

Question 5

What are fast signals?

Answer 5

Ion channels

Question 6

What are medium speed signals?

Answer 6

G protein coupled

Enzyme coupled

Question 7

What are slow signals?

Answer 7

Nuclear coupled- involve membrane soluble signal molecules binding to inactive receptor molecules and removing inhibitory proteins. The active receptors then travel to the nucleus and stimulate transcription of a target gene

Question 8

What are Wnt genes?

Answer 8

• 19 genes in mammals
• Many roles- cell shape, morphogenesis, stemness
• Involved in cell transformation, tumour progression and metastasis

Question 9

What is the Wnt protein?

Answer 9

• Coded by Wnt genes
• 350-400 aa
• Secreted insoluble so lipid modifications required (palmitoylation)
• Can act long range (morphogen) but is mainly a short range (cell-cell) signalling molecule
• When longe range it can be enclosed in a lipoprotein particle for easier transport

Question 10

What is Fz and LRP?

Answer 10

• Frizzled is a 7 transmembrane protein receptor for Wnt that binds Wnt through the cysteine rich domain
• Lipoprotein receptor related protein which is a single transmembrane protein and Wnt co-receptor required for B-catenin signalling

Question 11

How does signalling via Fz occur?

Answer 11

• Non-canonical Wnt

* Canonical Wnt

Question 12

What happens in canonical Wnt signalling?

Answer 12

Wnt binds to Fz/LRP
Phosphorylation of LRP occurs which causes APC complex to be localised to the membrane leading to its disassembly
B-catenin is not degraded and travels to the nucleus to induce a response

Question 13

What does B-catenin do in the nucleus?

Answer 13

• Displaces groucho from T cell factor/lymphocyte enhancer factor in the nucleus
• Recruits transcriptional complex
• Activates transcription of target genes

Question 14

What happens in non-canonical WNT PCP pathway?

Answer 14

• Fz recruits Dsh to the membrane
• Vangl recruits Prickle
• Prickle binding antagonises Dsh membrane association
• Fz/Dsh complex relocalises to opposite side of membrane
• Diego binds and protects Dsh stability by antagonising Prickle

Question 15

What is PCP?

Answer 15

Planar cell polarity: the coordinate polarisation and alignment of cells over many cell distances

Question 16

What does Flamingo do?

Answer 16

Binds Vangl and Fz and stabilises the complexes across membranes
It is essential for cell-cell contact to propagate PCP

Question 17

How does actin cytoskeleton regulation occur?

Answer 17

• Dsh activates Rho-GTPase which activates Rho-Kinase
• Leads to actin polymerisation on the same side of the cell
• To ensure actin polymerisation does not occur on the other side: Vang-Pk activate Mwh which inhibit it