Signal Transduction in Biological Membranes Flashcards Preview

ESA 2- Membranes and Receptors > Signal Transduction in Biological Membranes > Flashcards

Flashcards in Signal Transduction in Biological Membranes Deck (108):
1

What are G-Protein Coupled Receptors?

A family of receptors

2

How do G-protein coupled receptors act?

By altering the activity of effectors (e.g. enzymes / ion channels)

3

How do G-protein achieve alteration of effectors?

Via the activation of one or more types of guanine nucleotide binding proteins (G-proteins)

4

What are G-proteins responsible for?

A diverse range of cellular functions, including muscle contraction, stimulus-secretion coupling, catabolic and anabolic metabolic processes and light, smell, and taste perception

5

What is meant by G-proteins being heterotrimeric?

They are made up of three distinct subunits, alpha, beta and gamma.

6

Which sub-units in G-proteins bind tightly together?

ß and gamma

7

How do the ß and gamma sub units in G proteins function?

As a single unit

8

What does the α sub-unit of G proteins have?

A guanine nucelotide-binding site

9

What does the guanine nucleotide-binding site do?

Binds GTP and slowly hydrolyses it to GDP (GTPase activity)

10

How is G-protein present under basal conditions?

At the inner face of the plasma membrane, predominantly in its heterotrimeric form, with GDP bound to the α-subunit

11

What has a high affinity for G-protein under basal conditions?

Activated receptor (agonist bound)

12

What occurs when the activated receptor binds with the G-protein?

A protein-protein interaction occurs, leading to GDP being released by the α-subunit and binding GTP in it’s place

13

What does the activated G-protein receptors act as?

A guanine nucleotide exchange factor (GEF)

14

What happens once GTP has bound to the α-subunit of the G-protein?

The affinity of the receptor for both α-GTP and the ßγ  subunits is decreased

15

What is the result of the decreased affinity of α-GTP and ßγ  subunits?

Both are subsequently released, and are able to interact ith effectors

16

How is the effector interaction terminated?

By the intrinsic GTPase activity of the α-subunit hydrolysing GTP →  GDP

17

What happens once effector interaction has been terminated?

The affinity of the α-subunit for the ßγ  subunit increases, and the ßγ-subunit increases, and the αßγ heterodimer is reformed and awaits reactivation by an agonist-activated receptor to reinitiate cycle

18

What can G protein can be thought of as?

On/off switches and timers

19

What is the ‘on switch’ of G proteins?

Receptor-facilitated GDP/GTP exchange

20

What is the 'timer/off switch’ of the G proteins governed by?

The length of time taken for GTP hydrolysis

21

What did our understanding of G-protein mediated systems first come from?

Attempts to understand how hormones such as adrenaline brought about the formation of the second messnger cyclic AMP

22

Where does the G-protein have an intermediate role?

Where the stimulatory Gs stimulates adenylyl cyclase to produce cAMP

23

How are other pathways similar to the Gs pathway?

There are other, similar transduction pathways that employ a similar 3-component transduction pathway

24

What exists antagonistically to Gs pathways?

Inhibitory (Gi) pathways

25

What do Gi pathways do?

Reduced cAMP levels by inhibiting adenylyl cyclase

26

How are Gi proteins like Gs proteins?

They have additional effects independent of adenylyl cyclase inhibition, including effects on ion channels and signalling pathways involved in cell growth and differentiation

27

Have G-protein families that exert their actions on effectors other than adenylyl cylase been discovered?

Yes

28

What do Gq proteins do?

Preferentially interact with the membrane bound enzyme phospholipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to generate the second messengers 1,4,5-triphosphate (InsP 3 ) and diacylglycerol (DAG)

29

Where is rhodopsin present?

In mammalian retinal rod cells

30

What is the function of rhodopsin?

Light-sensing

31

What does rhodopsin do?

Activates a G protein (called transducing, or Gt), which in turn activates a phosphodiesterase enzyme that hydrolyses cylic GMP to 5’-GMP

32

What is the receptor for adrenaline/noradrenaline?

ß-adrenoreceptor

33

What is the G-protein for adrenaline/noradrenaline?

Gs

34

What is the effector for adrenaline/noradrenaline?

Stimulates adenylyl cyclase

35

What is the physiological response to adrenaline/noradrenaline?

Glycogenolysis, lipolysis

36

What is the receptor for acetylcholine?

M3-Muscarinic 
M2-Muscarinic

37

What is the G-Protein for acetylcholine when a M3 receptor is used?

Gq

38

What is the effector for acetylcholine when a M3 receptor is used?

Stimulates phospholipase C

39

What is the physiological response to acetylcholine when a M3 receptor is used?

Smooth muscle contraction

40

What is the G-protein for acetylcholine when a M2 receptor is used?

Gi

41

What is the effector for acetylcholine when a M2 receptor is used?

Inhibits adenylyl cyclase 
Stimulates K channel

42

What is the physiological response to acetylcholine when a M2 receptor is used?

Slowing of cardiac pacemaker

43

What is the receptor for light?

Rhodopsin

44

What is the G-protein for rhodopsin?

Gt

45

What is the effector for rhodopsin?

Stimulates cyclic GMP phosphodiesterase

46

What is the physiological response to light?

Visual excitation

47

What are the adrenergic receptors?

α1
α2
ß1
ß2

48

What G-protein α-subunit does the α1 receptor utilise?

Q

49

What G-protein α-subunit does the α2 receptor utilise?

I

50

What G-protein α-subunit does the ß1 receptor utilise?

S

51

What G-protein α-subunit does the ß2 subunit utilise?

S

52

What does stimulation of the α1 receptor do?

Stimulates phospholipase C

53

What does stimulation of the α2 receptor do?

Inhibits adenylyl cyclase

54

What does stimulation of the ß1 receptor do?

Activates adenylyl cyclase

55

What does stimulation of the ß2 receptor do?

Activates adenylyl cyclase

56

What are the cholinergic receptors?

M1
M2
M3

57

What G-protein α-subunit does the M1 receptor utilise?

Q

58

What G-protein α-subunit does the M2 receptor utilise?

I

59

What G-protein α-subunit does the M3 receptor utilise?

Q

60

What does stimulation of the M1 receptor do?

Activates phospholipase C

61

What does stimulation of the M2 receptor do?

Inhibits adenylyl cyclase

62

What does stimulation of the M3 receptor do?

Activates phospholipase C

63

How many Gα proteins does the human genome encode for?

20

64

How many Gß proteins does the human genome encode for?

5

65

How many Gγ proteins does the human genome encode for?

12+

66

How many combinations of Gα-γ are possible?

Over 1000

67

How many receptor types that can interact with Gα subtypes are there?

At least 800

68

How many enzyme/ion channel effectors can be activated/inhibited by interactions with Gα subunits and receptors?

10 or more

69

How do G-proteins bring about a specific cellular response?

An extracellular signal works via a specific GPCR to activate a single, or small sub-population of G-proteins and effectors in the cell

70

What can be used in the experimental manipulation of the G-protein cycle?

Cholera Toxin (CTx) and Pertussis Toxin (PTx)

71

What do CTx and PTx do?

They are enzymes that ADP-ribosylate specific G-proteins

72

What does CTx do specifically?

Eliminates the GTPase activity of G s α

73

What is the result of the elimination of the GTPase activity of G s α?

G s α is irreversibly activated

74

What does PTx do specifically?

Interferes with the GDP/GTP exchange on G i α

75

What is the result in the interference with the GDP/GTP exchange on G i α?

G i α becomes irreversibly inactivated

76

What can genetic changes in GPRCs result in?

Loss of function or gain of function mutations

77

Give 3 examples of conditions caused by mutations in GPCRs

Retinitis Pigmentosa
Nephrogenic Diabetes Insipidus
Familial Male Precocious Puberty

78

What causes Retinitis Pigmentosa?

A loss-of-function mutation to rhodopsin

79

What causes Nephrogenic Diabetes Insipidus?

A loss-of-function mutation to V2 vasopressin receptor

80

What causes Familial Male Precocious Puberty?

A gain-of-function mutation (receptor active without ligand) to the LH receptor

81

What is adenylyl cyclase?

An integral plasma membrane enzyme that can either be activated (via Gs) or inhibited (Gi) by activation of different receptors

82

What does adenylyl cyclase do?

Hydrolyses cellular ATP to generate cyclic AMP

83

What does cyclic AMP do?

Interacts with a specific protein kinase, which in turn phosphorylates a variety of other proteins within the cell to affect activity

84

What specific protein kinase does cyclic AMP interat with?

Cyclic AMP-dependent protein kinase (PKA)

85

What can receptors that activate adenylyl cyclase, and therefore increased cellular cyclic AMP levels, cause?

Increased glycogenolysis and gluconeogenesis in the liver
Increased lipolysis in adipose tissue 
Relaxation of a variety of types of smooth muscle 
Position inotropic and chronotropic effects in the heart

86

What is phospholipase C?

An enzyme that hydrolyses the membrane phospholipid (PIP 2 ) to IP 3

87

What is phospholipase C activated by?

Gq

88

How does IP 3  exert its effects?

By interacting with specific intracellular receptors on the endoplasmic reticulum to allow Ca 2+  to leave the lumen of the ER and enter the cytoplasm

89

What is cyclic GMP phosphodiesterase?

A specialised mechanism found in the photoreceptive cells of the retina

90

What does cyclic GMP phosphodiesterase do?

Regulates the breakdown of the second messenger cyclic GMP phosphodiesterase by Gt

91

What happens once a receptor has productively interacted with a G-protein?

The binding of the agonist is weakened, and agonist-receptor dissociation is likely to occur

92

What is the receptor susceptible to whilst activated?

A variety of protein kinases that phosphorylate the receptor and prevent it from activating further G-proteins

93

What is the problem with the activated receptor being susceptible to phosphorylation?

It compromises an important part of the receptor desensitisation phenomenon observed for most of the GPCR

94

What may the active lifetime of α-GTP be limited by?

Cellular factors that stimulate the intrinsic GTPase activity of the Gα subunit

95

What does the enzymatic activities in the cell favour?

The basal state

96

What is the result of enzymatic activities in the cell being such that the basal state is favoured?

Cells contain high activity enzymes that metabolise second messengers, rapidly returning their levels to the basal

97

How is the effect of second messenger/protein kinase activation opposed?

Enzymatic cascades are activated downstream that oppose the effect

98

What can the rate at which the sinoatrial node fires an action potential be affected by?

Ach release by the parasympathetic nerves

99

What is the predominant receptor in regulation of chronotropy in the heart?

M2 muscarinic cholinoceptors

100

What does activation of M2 muscarinic cholinoceptors cause?

An increase in the open probability of K+ channels via Gi

101

What does an increase in plasma membrane permeability to K+ cause?

Hyperpolarisation, slowing the intrinsic firing rate, resulting in a negative chronotropic effect

102

What is inotropy?

The force of heart contraction

103

What can influence inotropy?

Sympathetic innervation of the cardiac ventricles (and/or circulating adrenaline)

104

How is a positive inotropic effect in the heart bought about?

Activation of the ß-adrenoreceptors (predominantly ß1) increases the open probability of voltage operated calcium channels via Gs. 
Gs both interact directly with the VOCCs, and indirectly via cyclic AMP →  PKS →  phosphorylation and activation of VOCCs
The influx of Ca brings about a positive inotropic effect

105

How is arteriolar vasoconstriction bought about?

Sympathetic release of noradrenaline acts on α1-adrenoreceptors to stimulate phospholipase C and IP3 production via Gq
IP3 releases ER Ca, and initiates a contractile response

106

What can pre-synaptic GPCR influence?

Neurotransmitter release

107

Give an example of where pre-synaptic GPCR influence neurotransmitter release?

Pre-synaptic µ-opiod receptors can be stimulated, either by endogenous opiods or by analgesics such as morphine to couple Gα1 proteins

108

How is neurotransmitter release reduced by GPRCs?

The Gßγ subunits are liberated from the heterodimer and interact with VOCCs to reduce Ca entry, thus reducing neurotransmitter release