What is autocrine signalling?
Signals a cell gives to itself
What is paracrine signalling?
Signals a cell gives to neighbouring cells e.g local mediators, membrane bound signals and neurotransmitters
What is endocrine signalling?
Signals a cell gives to cells in different locations e.g hormones
What is the cell signalling cascade?
Extracellular signal molecule Receptor protein Intracellular signalling proteins Effector proteins Response
What are fast signals?
Ion channels
What are medium speed signals?
G protein coupled
Enzyme coupled
What are slow signals?
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
What are Wnt genes?
- 19 genes in mammals
- Many roles- cell shape, morphogenesis, stemness
- Involved in cell transformation, tumour progression and metastasis
What is the Wnt protein?
- 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
What is Fz and LRP?
- 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
How does signalling via Fz occur?
- Non-canonical Wnt
* Canonical Wnt
What happens in canonical Wnt signalling?
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
What does B-catenin do in the nucleus?
- Displaces groucho from T cell factor/lymphocyte enhancer factor in the nucleus
- Recruits transcriptional complex
- Activates transcription of target genes
What happens in non-canonical WNT PCP pathway?
- 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
What is PCP?
Planar cell polarity: the coordinate polarisation and alignment of cells over many cell distances
What does Flamingo do?
Binds Vangl and Fz and stabilises the complexes across membranes
It is essential for cell-cell contact to propagate PCP
How does actin cytoskeleton regulation occur?
- 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
