CellSig15 - 28 Flashcards Preview

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Flashcards in CellSig15 - 28 Deck (28):
1

What targets Hh to the PM?

N-terminal sequence

2

What removes the N-terminal sequence of Hh?

C-terminal end

3

What happens to the C-terminal end of Hh after cleaving off the N-terminus?

Cholesterol coupling

4

What occurs to the N-terminal end of Hh after cleavage?

Palmitoylation

5

What adds palmitoyl to Hh?

Ski in Drosophila, Hhat in vertebrates

6

What do the modifications of Hh make it?

Highly hydrophobic - a problem for it trying to leave the membrane

7

What overcomes the hydrophobicity of Hh?

Dispatched and Scube - create multimeric Hh particles, or load Hh onto lipoprotein particles

8

What is required for long term transmission of Hh?

HSPGs

9

Characterise Ptc

12TM protein, similar to dispatched

10

What does Ptc do?

Inhibits Smo

11

What occurs when Hh binds Ptc?

Ptc inhibits its inhibition, so Smo is activated

12

What is the relationship stoichiometrically between Ptc and Smo?

Many Smo for each Ptc

13

What effect does Ptc have on Smo trafficking?

In absence of Hh, Smo is internalised

14

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

15

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.

16

Molecule that can interfere with Smo

Cyclopamine

17

Who proposed the current model of Hh signalling, and when?

Hooper and Scott, 2005

18

What transcription factor is involved in Hh signalling?

Ci - cubitus interruptus

19

What occurs in the absence of Hh?

Two complexes keep Ci out of the nucleus - Cos2/Fused/Ci (bound to Smo) and SUFU/Ci. CKI/PKA/GSK3 acts on Ci, bringing Slimb which shortens Ci to CiR. CiR represses Hh target genes

20

What occurs in the presence of Hh?

Hh releases Ci from the two precursor complexes

21

How does the CKI/PKA/GSK3 complex prep Ci for Slimb interaction?

PKA phosphorylates first, priming for phosphorylation by GSK3 and CK1

22

What is Slimb?

F box protein - component of SCF unbiquitin E3 ligase complex

23

Positive regulators of Hh signalling?

CDO/BOC/GAS-1

24

What does Hhip do?

Binds Hh, limiting diffusion

25

What is interesting about Gli1?

Feedsforward - can only activate the Hh pathway

26

What are the mammalian homologues of Ci?

Gli1-3

27

What does Hh form in the developing limb?

Zone of polarizing activity - conferring posterior identity

28

What major conditions is Hh implicated in?

Holosprosenchephaly, syndactyly, cancers, Gorlin syndrome