CellSig15 - 28 Flashcards
What targets Hh to the PM?
N-terminal sequence
What removes the N-terminal sequence of Hh?
C-terminal end
What happens to the C-terminal end of Hh after cleaving off the N-terminus?
Cholesterol coupling
What occurs to the N-terminal end of Hh after cleavage?
Palmitoylation
What adds palmitoyl to Hh?
Ski in Drosophila, Hhat in vertebrates
What do the modifications of Hh make it?
Highly hydrophobic - a problem for it trying to leave the membrane
What overcomes the hydrophobicity of Hh?
Dispatched and Scube - create multimeric Hh particles, or load Hh onto lipoprotein particles
What is required for long term transmission of Hh?
HSPGs
Characterise Ptc
12TM protein, similar to dispatched
What does Ptc do?
Inhibits Smo
What occurs when Hh binds Ptc?
Ptc inhibits its inhibition, so Smo is activated
What is the relationship stoichiometrically between Ptc and Smo?
Many Smo for each Ptc
What effect does Ptc have on Smo trafficking?
In absence of Hh, Smo is internalised
Outline how Ptc effects Smo trafficking in mammals
In the primary cilium - no Hh, Ptc localised to cilium; Hh, Ptc leaves and Smo can move in
Why is Ptc thought to be a pump?
Homology to prokaryotic permeases (pump out toxins); is related to NPC1, mutations in which cause uptake of fatty deposits on organs; C. elegans has Ptc-like proteins, but no Hh.
