Exley cell signalling lecture 3 Flashcards Preview

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Flashcards in Exley cell signalling lecture 3 Deck (16)
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1
Q

How is Ins(1,4,5)P3 formed?

A

Receptor-activated hydrolysis of

phosphatidylinsitol (4,5) bisphosphate / PIP2

2
Q

What is the function of Ins(1,4,5)P3 in cells?

A

Acts as a receptor for release of Ca2+ from specialized intracellular stores
And regulates the flow, through a high conductance channel

3
Q

What do IP3 induced sparks and puffs represent?

A

Highly localized Ca2+ release from the ER through ryanodine receptors and inositol trisphosphate receptors

4
Q

Variability in the sensitivity of individual receptors to Ins(1,4,5)P3 is an important factor in determining…….?

A

If the quanta of Ca2+ release are fated to remain localized or to produce regenerative waves which sweep across the whole cell.

5
Q

What are the 3 ways in which sensitivity to stimulation via Ins(1,4,5)P3 is achieved?

A

1) Receptor clustering
2) at least 3 different classes of Ins(1,4,5)P3, with different sensitivities to the agonist
3) Rate of metabolism of InsP3

6
Q

What happens to the behaviours of the inositol trisphosphate receptor channels in the presence of

a) Low agonist stimulaion
b) Higher agonist stimulation
c) Very high agonist stimulaton

A

a) Few receptors bind InsP3. High localized Ca2+ ‘blips’ signals are generated from cytoplasmic Ca2+
b) Coordinated openings of several InsP3 channels within a cluster, stimulating gating of nearby channels - Ca2+ induced Ca2+ release
c) Propogation of Ca2+ waves, due to release at adjacent clusters, diffusion and CICR.

7
Q

What structural change occurs within IP3 when Ca2+ is bound and why?

A

Large-scale relocations of IP3 binding domains.
IP3 binding cores ligand with IP3 -> Lys-C digestion
= Windmill structure

8
Q

Give some cellular processes what the IP3/Ca2+ signalling pathway is involved in

A

Metabolism, Fertilization, Exocytosis, Proliferation, Differentiation, Aldosterone secretion, Ion channel opening, Aggregation, Neuronal synaptic pasticity, Fluid secretion, Muscle contraction…

9
Q

What are the stages of mammalian fertilization in relation to IP3/Ca2+?

A

1) Sperm chemotaxis and acrosome reaction
2) PLC injected into the occyte
3) PLC binds to PIP2
4) PIP2 ligand binds to IP3
5) Cytosolic calcium oscillator -> Ca2+ oscillations
6) Oocyte activation and cell proliferation

10
Q

What is the role of the IP3/Ca2+ signalling pathway in regulating gene transcription and proliferation in T cells?

A

1) Antigen binds to TCR
2) PLC-1 binds to PIP2
3) PIP2 binds to IP3
4) IP3 binds to IP3 receptor on endoplasmic reticulum
5) Direct release of Ca2+ and stimulation of CRAC Orai 1 channel -> Calcineurin
6) Release of NFAT
7) Gene transcription and proliferation

11
Q

What Ca2+ activated channels are responsible for pacemaker depolarization, which trigger the action potentials that control breathing?

A

TRPM4 channels

12
Q

Ins(1,4,5)P3 is metabolised into Ins(1,3,4,5)P4 - by what enzyme?

A

Ins(1,4,5)P3 3-kinase.

13
Q

How many isoforms of the Ins(1,4,5)P3 3-kinase enzyme are there? What 2 regulated by?

A

3

Ca2+/calmodulin-dependent protein kinase II (CAMKII).

14
Q

What is the definition of a kinase?

A

an enzyme involved in the transfer of a phosphate group (phosphotransferase) without regeneration of the donor molecule

15
Q

In vivo, what does a pool of Ins(1,3,4,5)P4 protect against and why?

A

protects against the hydrolysis of Ins(1,4,5)P3
because it has a ten-fold higher affinity for the enzyme (inositol phosphate 5 phosphatase) whose major activity is the hydrolysis of inositol phosphates.

16
Q

What is the definition of a phosphatase?

A

catalyse the hydrolysis and the synthesis of organic esters of phosphoric acid; they transfer phosphate groups from one molecule to another