Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ICPP > Session 2: Intracellular Signalling > Flashcards

Session 2: Intracellular Signalling Flashcards

1
Q

Receptors for what type of molecules are intracellular?

A

Steroid

Thyroid Hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

1) Reception
2) __________
3) Response

A

Transduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the three “superfamilies” of CELL SURFACE receptors?

A

GPCRs
Ligand-gated ion channels
Enzymatic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define the term ‘agonist’

Define in terms of affinity and efficacy also

A

Something that binds to the receptor and ACTIVATES it, leading to signal transduction events.
Agnoists bind with affinity AND efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Define the term ‘antagonist’

Define in terms of affinity and efficacy also

A

Something that binds to the receptor but DOES NOT activate it, blocking the effects of the agonist at the receptor.
Antagonists possess affinity but do not possess efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

GPCRs consist of how many transmembrane domains?

A

7 TM domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

GPCRs have an extracellular _____ -terminal

A

N-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

GPCRs have an intracellular _____-terminal

A

C-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Each GPCR has it’s own unique _______ ________ sequence, ranging from _____ - _______ in length

A

Amino acid

300-1200

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many regions of GPCRs are responsible for ligand binding? What are formed by?

A

2
Formed by either:
2-3 transmembrane domains
or -N terminal region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

An activated GPCR must interact with another protein called a what?

A

Guanine-nucleotide binding protein (G- protein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

G proteins are made up of how many subunits?

They are therefore be defined as what?

A

3 subunits

Heterotrimeric

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Though made up of 3 subunits, functionally how many subunits does a G protein have?

A

Two functional subunits

“Dimeric”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the three subunits of G proteins and how are they arranged?

A

Alpha, Beta, Gamma
Alpha is associated to the Beta Gamma subunit.
The alpha subunit dissociates from the beta gamma subunit upon binding of agonist but the beta and gamma subunits do not dissociate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

When an agonist binds to a GPCR what happens in order to generate a downstream signal?

A
  • Agonist binds to GPCR on cell surface
  • GPCR exchanges a GTP for a GDP on the alpha subunit
  • The alpha, beta, gamma complex dissociates into alpha bound to GTP and beta gamma subunits
  • Each of these subunits can then interact with effector proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What feature of the receptor, G-protein and the effector increases the efficacy of the effector protein response?

A

They are all co-localised to the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Most diseases are caused by inefficient ______ of the G-protein signalling

A

“Turn- off”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is G-protein signalling terminated?

A

GTPase activity of the alpha subunit which hydrolyses GTP back to GDP. The alpha-GDP and beta gamma subunits then reform an inactive heterodimeric complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Is the alpha subunit a good or a poor GTPase?
Does it hydrolyse GTP quickly or slowly?
What does this mean in terms of signalling?

A

The alpha subunit is a poor GTPase
It hydrolyses GTP slowly
This means that there is a sufficient period of time for the alpha and beta gamma subunits to pass on their signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the three types of G- protein based on the G alpha subunit?

A

Galphai
Galphas
Galphaq

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the effector proteins involved with each G protein subtype and are they inhibitory or stimulatory

A

Galphai inhibits adenylyl cyclase
Galphas stimulates adenylyl cyclase
Galphaq stimulates phospholipase C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the acronym to help remember these types of G-protein and their receptors?

A

Q- alpha 1
I-alpha 2 These are Sympathetic
S-beta 1
S-beta 2

Q- musclarinc 1 These are Parasympathetic
I- musclarinic 2/4
Q- musclarinic 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Name two toxins that interfere with G protein function

A 
Cholera toxin (CTx)
Pertussis toxin (PTx)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does CTx infer it’s toxicity in the cell?

A

It modifies all the Gs containing proteins and means that they can no longer hydrolyse GTP. They are therefore permanently switched “on” leading to extremely hightened cAMP production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How does PTx infer it’s toxicity in the cell?

A

It modifies a Gi protein and does not allow it to be stimulated, it cannot dissociate and is therefore not activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

If some examples of second messengers

A

cAMP, IP3 and DAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the role of adenylyl cyclase once it is activated in cells?

A

Converts ATP into cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the role of Phospholipase C?

A

The convert PIP2 into IP3 and DAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Effectors can be ___________ or ___________

A

Enzymes or Ion channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Once cAMP is produced through the activity of adenylyl cyclase, what happens?

A

cAMP activates Protein Kinase A (PKA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

PKA is a hydro______ molecule that is readily available in what part of the cell?

A

hydroPHILIC

In the cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the structure of Protein Kinase A?

A

Made up of 4 subunits: 2 Regulatory subunits (R) and 2 Catalytic subunits (C)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is the role of the R subunits in Protein Kinase A?

A

To regulate the activity of the C subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the role of the C subunits in Protein Kinase A?

A

To regulate the catalytic activity of Protein Kinase A (PKA) by phosphorylating target proteins in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What happens when cAMP levels are increased?

A

They bind to the R subunits and cause the C subunits to dissociate and phosphorylate target proteins in the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Phopholipase C converts PIP2 into what?

A

IP3 nd DAG

37
Q

What are the basal levels of free Ca2+ in the main extracellular sites?

A

1mM

10^-3 M

38
Q

What are the basal levels of free Ca2+ in the main intracellular sites i.e. the “stores”: SER/ER?

A

1mM

10^-3 M

39
Q

What are the basal levels of free Ca2+ in the cytosol of cells i.e. the “sink”?

A

100nM

10^-7 M

40
Q

________ can also be regarded as an intracellular Ca2+ store but this is more to BUFFER excess Ca2+ than to act as an functional reservoir

A

Mitochondria

41
Q

Intracellular stores of Ca2+ reaches _____ concentrations to provide the cell with access to a large reservoir source when required

A

high

42
Q

Smooth endoplasmic reticulum (SER) store is known as a rapid or non-rapid release store?

A

Rapid response

43
Q

Which Ca2+ store is known as non-rapid release store?

A

Mitochondria

44
Q

Calcium is a divalent (or bivalent) meaning what?

A

It has a valance of two and therefore forms two chemical bonds

45
Q

Why is calcium’s divalent nature important for its role aa a messenger?

A

It means that it is attracted to points on biological molecules that are negatively charged or polarised

46
Q

What is distinctive about the election clouds on calcium?

A

They are ‘polarisable’ or ‘squishy’ meaning they can be easily distorted- can fit into irregular/enclosed spaces

47
Q

What is the advantage of the large ionic gradients of calcium between the cytosol, SER/SR/mitochondrial stores and extracellular calcium?

A

Large changes in the cytosolic sink concentration can be achieved with relatively small movement of calcium from the two major stores
I.e. relatively little needs to be removed from the cytosol to get back to basal levels

48
Q

Ca2+ concentration is much greater ________ the cell compared to _______ the cell

A

Outside

Inside

49
Q

Cell membranes are normally ___________ to Ca2+ can only access the interior of the cell through highly selective _________/________

A

Impermeable

channels/transporters

50
Q

Name the three major routes of calcium through the plasma membrane

A

Voltage-gated calcium channels (VGCCs)
Ligand-gated ion channels (LGICs)
Store-operated channels (SOCs)

51
Q

Voltage-gated ion channels open in response to what?

A

Depolarisation

52
Q

Most ligand-gated ion channels are activated by what kind of molecules?

A

Neurotransmitters

53
Q

Store operated channels are distinctive Ca2+ channels with very low __________ that operate over hours, minutes or seconds?

A

Conductances

Seconds

54
Q

Store operated channel conductance is relatively slow or fast compared to other channels?

A

Slow

55
Q

Are SOCs expressed in excitable or non-excitable cells?

A

Both

56
Q

In non-excitable cells, SOCs are important for what?

A

Accessing extracellular Ca2+ when SER stores for Ca2+ are depleted

57
Q

SOCs are important in _______ muscle where prolonged states of stable _______ are required

A

smooth

contraction

58
Q

The plasma membrane contains two very important carriers for Ca2+ that contribute to re-establishing the very low cytosolic basal Ca2+ concentration of _____.
What are they?

A

10^-7
Plasma Membrane Calcium ATPase (PMCA)
Sodium-Calcium Exchanger (NXC)

59
Q

The PMCA is expressed in which cell types?

A

All cells

60
Q

The PMCA uses how many molecules of ATP per ion of Ca2+ out of the cell?

A

One

61
Q

The PMCA transfers Ca2+ from where to where?

A

From the cytosol to the extracellular space

62
Q

Doe the PMCA have a high or low affinity for Ca2+?

A

High affinity

63
Q

What is Calmodulin?

A

A calcium sensor

64
Q

Is PMCA’s expression in cells normally quite high or low?

A

Low

65
Q

PMCA’s general role is to “____________” intracellular Ca2+ concentration regulation

A

Fine-tune

66
Q

What is NCX?

A

Sodium-Calcium exchanger

67
Q

Does NCX require ATP?

A

No

68
Q

How does the NCX work if it does not use ATP directly?

A

Uses the electrochemical energy gradient provided by the large concentration of extracellular Na+

69
Q

The NCX exchanges _____ Na+ into the cell for every ______ Ca2+ pumped out

A

3

1

70
Q

Following the work of the NCX, how are the intracellular and extracellular levels of Na+ restored?

A

The Sodium/Potassium (Na+/K+) ATPase

71
Q

The NXC has a ______ affinity for Ca2+ than PMCA, but is expressed in ______ cell types.

A

Low

Many

72
Q

Which NCX has a relatively ____ affinity for Ca2+, it has a _______ capacity for pumping Ca2+ out of the cell when required

A

Low

High

73
Q

Compared to the PMCA, _____ is considered to act as the primary pump of Ca2+ when levels are over _______

A

NCX

10 microM

74
Q

NCX is especially active in which tissues?

A

Excitable tissues such a muscle and nerve

75
Q

What happens to the NCX in heavily depolarised cells?

A

The NCX is reversed and therefore pumps Ca2+ into the cell and pumps Na2+ out to rectify the increased concentration of intracellular Na+

76
Q

Which three receptors are involved in controlling the release of Ca2+ from the SER/SR intracellular “store” into the intracellular cytosolic “sink”?

A

GPCR (Gq types) in the plasma membrane
IP3 receptors in the SER/SR membrane
Ryanodine (Ryr) receptors in the SER/SR membrane

77
Q

What type of GPCR contributes to the regulation of Ca2+ efflux from intracellular stores?

A

Gq type GPCRs

78
Q

In brief, explain what happens when an agonist binds to the Gq receptor type at the plasma membrane

A

-Phospholipase C (PLC) is activated by the alpha q subunit
-PLC cleaves PIP2 in the plasma membrane into IP3 and DAG
-IP3 then binds to IP3 receptors on the SER/SR membrane and activates them
-Leads to a large increase in intracellular Ca2+ released from the SER/SR
(-DAG activates PKC which activates its own substrates within the cell)

79
Q

Why is it so important that intracellular levels of Ca2+ return to basal levels as soon as possible once they are raised?

A

Prolonged increased Ca2+ concentration in the cytoplasm can lead to cell death

80
Q

What type of receptor is the IP3 receptor?

A

Ligand gated ion channel

81
Q

What happens when IP3 binds to the IP3 receptor on the SER/SR membrane?

A

The IP3 receptor ion channel opens and allows Ca2+ efflux out of the SER/SR and into the cytosol

82
Q

IP3 receptor activity remains _________ to the Ca2+ level driving the synthesis of IP3

A

Proportional

83
Q

Which route is the main way in which GPCR activation signalling via increases in IP3 causing an increase in cytoplasmic Ca2+?

A

Binding of IP3 to IP3 receptors in the SER/SR membrane

84
Q

What type of receptors are Ryanodine receptors (RyRs) ?

A

Ligand gated ion channels

85
Q

IP3 and DAG are examples of what?

A

Second messangers

86
Q

RyRs are expressed across cell types and are heavily expressed in the _____ of muscle cells

A

Sarcoplasmic reticulum (SR)

87
Q

The activation of RyR channels varies in the three major muscle types which are…

A

Smooth, Skeletal, Cardiac

88
Q

In smooth and cardiac muscle, the triggering calcium signal comes through the activation of which signalling molecule targets?

A

Voltage-operated Calcium Channels (VOCCs)

ICPP (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions