Lecture 8 Flashcards
Where does wnt derive its name from
Amalgam of wingless Drosophila gene and Int vertebrate proto-oncogene
Int-1 is a proto-oncogene, what causes its activation
Integration of the mouse mammary gland tumour virus
Wingless (wg) mutants initially discovered produced wingless but viable flies, T or F
T
Explain how wg and hh maintain each other’s expression in an auto-regulatory loop
Wg maintains hh by controlling the expression of engrailed (en), a transcription factor that regulates hh expression. Hh then in-turn maintains and directly upregulates wg
What is significant about hh and wg knockout mutants
They exhibit the same phenotype – larvae with a lawn of denticles
Unlike similar developmental signalling pathways, wnt expression is highly conserved throughout Kingdom Animalia, T or F
T – even found in sponges
Why is it that vertebrates have more wnt genes
Due to genome duplication throughout evolution
The wnt protein is produce by a cleavage event that separates its signalling sequence from the initially translated protein, T or F
T
What is the role of porcupine in the early modification of wnt
Porcupine is an acyl transferase that adds palmitoleic acid modifications to a serine residue at point 209 in the wnt3a structure
What is the hypothesised role of wntless in wnt signalling and what is its basic structure
Wntless is a 7 transmembrane domain protein potentially required for the transport of wnt to the plasma membrane and its subsequent release/presentation to target cells
What is the effect of palmitoylation and palmitoleic acid modification of the wnt protein
Addition of these hydrophobic groups makes wnt insoluble in water
What components of the extracellular matrix are involved in mediating the diffusion of wnts away from the sending cell
Heparan sulphate proteoglycans (HSPGs)
What is significant about the fact that most of the effects of Wnt signalling can be elicited by a membrane bound form of the protein in Drosophila
It suggests that wnts act as juxtacrine signalling molecules or that they don’t diffuse far and act on adjacent cells in Drosophila
Recall the two main receptors involved in reception and transmission of wnt signalling in Drosophila
Frizzled and Arrow
What is the name of the nuclear factor in Drosophila that is induced as a result of wnt signalling and its corresponding vertebrate homologue
Armadillo (vertebrate homolog – ?-catenin)
What are the names of the arrow receptor homologues found in humans
LRP5 and 6