Lecture 5 - G Protein Coupled Receptor Mediated Signalling Flashcards

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1
Q

2 key types of receptor?

A

GPCR and enzyme linked receptors.

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2
Q

How many transmembrane domains do GPCRs have?

A

Seven.

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3
Q

Give an example of a GPCR.

A

Beta adrenergic receptor. Ligand = adrenaline, which binds to the extracellular side between TM helices 3,5 and 6. Possesses a lipid end that anchors the C-terminus to the membrane. Couples to G proteins via the 5 and 6 TM helices.

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4
Q

GPCRs couple to trimeric G proteins that consist of?

A

An alpha, beta and gamma subunit.

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5
Q

There are multiple classes of trimeric G proteins, the main one being Gs, which activates adenylate cyclase. Other classes?

A
Golf = involved in smell. 
Gi = inhibits adenylate cyclase. 
Go/q = activate the PLC/Ca2+ pathway. 
Gt = transducin. Coupled to photoreceptors.
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6
Q

Inactive G proteins are tightly bound to GDP. How does nucleotide exchange occur?

A

Guanine nucleotide exchange factor (GEF).

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7
Q

An active G protein (GTP bound) has a low GTPase activity. How is this enhanced?

A

GTPase activating protein (GAP) is used for hydrolysis.

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8
Q

Upon activation Galpha subunit can interact with target proteins on the membrane. Give an example.

A

Adenylate cyclase.

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9
Q

Provide examples of some secondary messengers in signalling cascades.

A

cyclic AMP (cAMP), Ca2+, 1-2-diacylglycerol.

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10
Q

What are secondary messengers?

A

Small molecules produced upon activation that usually amplify a signalling cascade. They have their own secondary messengers.

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11
Q

How was cAMP discovered?

A

Liver cells were fractionated to separate the cytoplasm and the membrane. The membrane contains the GPCR, G proteins and adenylate cyclase, whilst the cytosol contains the glycogen phosphorylase.

Adrenaline added to the membrane solution and cAMP produced. cAMP then added to cytosol –> glycogen phosphorylase activated. This is proof that a small molecule transfers the signal.

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12
Q

How does cAMP function?

A

It activates protein kinase A (PKA).

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13
Q

Glycogen metabolism - what breaks down glycogen?

A

Glycogen phosphorylase.

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14
Q

Glycogen metabolism - what synthesises glycogen?

A

Glycogen synthase.

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15
Q

Effects of cAMP on glycogen degredation?

A
  • Adrenaline activates G protein, binds to adenylate cyclase.
  • Activates the synthesis of cAMP.
  • cAMP activates PKA, which phosphorylates glycogen phosphorylase kinase (GPK).
  • Glycogen phosphorylase is phosphorylated by GPK and glycogen breakdown is activated.

ALSO:

  • PKA phosphorylates protein phosphatase (PP) = inactivated.
  • PP is responsible for the removal of the phosphate from glycogen phosphorylase and GPK, inactivating them both.
  • PKA phosphorylates glycogen synthase = inactivated.
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16
Q

The role of PKA and PP in glycogen synthesis?

A

cAMP does not activate PKA. Since PKA is inactive, PP is active. PP removes the phosphate from glycogen phosphorylase and GPK, inactivating them both.

PP will dephosphorylate glycogen synthase = activated.

17
Q

How do cells maintain a low level of calcium in their cytosol, compared to outside the cell/in the ER?

A

Difference maintained by calcium ATPases –> pump calcium out of the cell/into organelles.

18
Q

Calcium channels on the p. membrane/ER when activated provide an increase in cytosolic Ca2+. Occurs when required as a secondary messenger. Name the channels on each membrane.

A

Plasma membrane channels: CRAC and P2X.

ER channels: IP3R. ER channels have a clacium pump, SERCA, that constantly removes excess cytosolic calcium.

19
Q

Examples of calcium signalling?

A

Muscle contraction and NT release.