Brainscape's Knowledge GenomeTM

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


See full index

Membranes and Receptors > Signal transduction > Flashcards

Signal transduction Flashcards

1
Q

Why is signal transduction important?

A

Although some receptors can directly alter cellular activity, many require “transduction” of the initial ligand binding event via other intracellular signalling components to generate a response, e.g. contraction, secretion, proliferation, differentiation, etc.

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

Give 2 examples of intracellular receptors.

A

Steroid hormone receptors, thyroid hormone receptors

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

Why are most receptors located on the cellular surface?

A

The majority of extracellular signalling molecules do not readily cross the plasma membrane

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

Name 3 extracellular signalling molecules.

A

Hormones, neurotransmitters, growth factors

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

What needs to be present in order for cells to respond to extracellular signals?

A

The appropriate receptor

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

What are the 3 steps in signal transduction?

A

Reception
Transduction
Response

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

What are the 3 superfamilies of cell surface receptor?

A

• Ligand-gated (receptor-operated) ion channels
(e.g. nicotinic acetylcholine receptors)
• Receptors with intrinsic enzymatic activity
(receptor tyrosine kinases (e.g. insulin receptor)
• G protein-coupled (7TM) receptors
(e.g. muscarinic acetylcholine receptors)

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

What does ligand binding do to a receptor?

A

Activates the receptor, which in turn directly or indirectly

brings about a change in cellular activity

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

How do ligand gated ion channels work?

A

Ligand binding „gates‟ the channel to allow ions to move into or out of the cell

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

How do receptors with intrinsic enzymatic activity work?

A

Ligand binding activates an enzyme activity (e.g. tyrosine

kinase) that phosphorylates the receptor itself + other substrates

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

Describe the insulin receptor.

A

Heterotetramer (2 alpha and 2 beta subunits)
Alpha subunit- insulin binding
Beta subunits contain enzymatic activity
Phosphorylate tyrosine residues on each other when insulin binds

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

Why, clinically, is it important to know about how GPCRs work?

A

Currently ~40% of all available prescription drugs exert their therapeutic effects directly (as agonists or antagonists) or indirectly at GPCRs

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

What does an agonist do to a GPCR?

A

Bind to the receptor and activate it

leading to intracellular signal transduction events

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

What does an antagonist do to a GPCR?

A

Bind to the receptor but do not activate it

block the effects of agonists at the receptor

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

How are GPCR agonists used therapeutically?

A 
Anti-asthma:
β2 adrenoceptor agonists
SALBUTAMOL, SALMETEROL
Analgesia/anaesthesia:
μ-opioid receptor agonists
MORPHINE, FENTANYL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How are GPCR antagonists used therapeutically?

A 
Cardiovascular (e.g. hypertension):
β adrenoceptor antagonists
PROPRANOLOL, ATENOLOL
Neuroleptics (e.g. anti-schizophrenic):
D2 dopamine receptor antagonists
HALOPERIDOL, SULPIRIDE
17
Q

What is clopidogrel?

A

An anti platelet drug (newish)
Used for coronary artery disease/ MI prevention
Irreversible antagonist at PY12 purinoceptor
Warnings being flagged- may have some problems

18
Q

What is aripiprazole?

A 
Anti schizophrenic (atypical). Also used in unipolar and bipolar depression
D2Rs (partial agonist- weak agonistic action)
19
Q

What are the therapeutic applications of drugs targeting GPCRs in the CNS?

A 
Depression 
Schizophrenia 
Psychosis 
Parkinson‟s disease
Migraine
20
Q

What are the therapeutic applications of drugs targeting GPCRs in the CVS?

A

Hypertension
Congestive heart failure
Cardiac arrhythmia
Thrombosis

21
Q

What are the therapeutic applications of drugs targeting GPCRs in the respiratory system?

A

Asthma

Chronic obstructive pulmonary disease (COPD)

22
Q

What are the therapeutic applications of drugs targeting GPCRs in the gastrointestinal system?

A

Acid reflux
Gastric ulcer
Nausea

23
Q

What are the therapeutic applications of drugs targeting GPCRs in the genitourinary system?

A

Overactive bladder
Prostate cancer
Benign prostatic hyperplasia

24
Q

What are other general therapeutic applications of drugs targeting GPCRs?

A 
Chronic pain
Glaucoma
Rhinitis
Motion sickness
Anaphylaxis
25
Q

What do mutations to G protein-coupled receptors result in? Give 3 examples.

A

Genetic changes to GPCRs result in loss-of-function or gain-of-function mutations, e.g.

  • Retinitis pigmentosa can be caused by a loss-of-function mutation to rhodopsin
  • Nephrogenic diabetes insipidus can be caused by a loss-of-function mutation to the V2 vasopressin receptor
  • Familial male precocious puberty is caused by a gain-of-function mutation to the luteinizing hormone (LH) receptor
26
Q

What are the different stimuli that GPCRs can respond to?

A

-Sensory GPCRs sense light (e.g. rhodopsin), odours and tastes
Different GPCRs can also respond to:
• Ions (H+, Ca2+)- these may also be called proton/ acid sensing GPCRs
• Neurotransmitters (e.g. acetylcholine, glutamate, dopamine, GABA)
• Peptide and non-peptide hormones (e.g. glucagon, adrenaline)
• Large glycoproteins (e.g. thyroid-stimulating hormone (TSH))

27
Q

How many different GPCRs have been identified in the human genome?

A

Over 800 ( in lecture he said around 865). This accounts for over 2% identified genes.

28
Q

What is the basic structure of all GPCRs?

A
  • Single polypeptide chain (300-1200 amino acids)
  • 7-transmembrane (7TM)- spanning regions
  • Extracellular N-terminal
  • Intracellular C-terminal
29
Q

Where are the 2 regions in GPCRs where ligand binding occurs?

A
  • For some receptors the ligand binding site is formed by (2-3 of) the transmembrane (TM) domains (binding pocket is between the domains of the receptor.
  • In other cases the N-terminal region (and other extracellular domains) form the ligand binding site (e.g. peptides, polypeptides and glutamate.
30
Q

How do GPCRs respond to ligands?

A

By changing conformation sufficient to attract another protein (G-protein)

31
Q

How do GPCRs elicit an intracellular response?

A
  • An activated GPCR must interact with another protein called a guaninenucleotide binding protein (G protein)
  • G proteins are made up of three subunits ( they are „heterotrimeric‟): α (alpha), β (beta) and γ (gamma) (beta and gamma subunits are functionally dimeric (stay together)
  • The GPCR-G protein interaction activates the G protein by causing GTP to be bound instead of GDP on the G protein α subunit
  • The α-βγ complex immediately dissociates (into α-GTP + free βγ subunits) and each can then interact with effector proteins (second messenger-generating enzymes, or ion channels)
  • The α-GTP and/or βγ interaction with effectors lasts until the α subunit GTPase activity hydrolyses GTP back to GDP. α-GDP and βγ subunits then reform an inactive heterotrimeric complex.
32
Q

Why does the alpha G-protein subunit dissociate from the beta-gamma subunit during activation?

A

When GTP is bound to the alpha subunit, it loses its affinity for the beta-gamma subunit.

33
Q

What makes the G-protein subunits reassemble after activation?

A

After activation, the alpha subunit hydrolyses the bound GTP to GDP with its intrinsic enzymatic activity.
The GDP bound alpha subunit regains its affinity for the beta-gamma subunit. This terminates its actions on downstream effectors.

34
Q

How is the length of a GPCR signal regulated?

A

GTPase activity on the alpha subunit can be regulated. Timer function controls the gain of the signal (how long the signal lasts)

35
Q

What gives rise to the diversity of GPCRs?

A

The human genome encodes 20 Gα (alpha), 5 Gβ (beta)
and 12+ Gγ (gamma) proteins
Therefore, there are >1000 possible Gα-βγ protein combinations

36
Q

What governs Receptor-G protein selection?

A

Activated GPCRs preferentially interact with specific types of G protein. The Gα subunit is a primary determinant.
In turn, Gα subunits and Gβγ subunits interact with specific effector proteins.

37
Q

How does Receptor-G protein selection give rise to specificity?

A

It means that an extracellular signal, working via a specific
GPCR, will activate a single, or small sub-population of G
proteins and effectors in the cell to bring about a
specific cellular response.

38
Q

Give specific examples of GPCRs, their stimulus, G-proteins and their response.

A
  • adrenaline/ noradrenaline- β-adrenoceptor: Gsα, (Gβγ) (upregulates) adenylyl cyclase
  • adrenaline/noradrenaline- α2-adrenoceptor: Giα, (Gβγ) (downregulates) adenylyl cyclase
  • adrenaline/ noradrenaline- α1-adrenoceptor: Gqα, (Gβγ) (upregulates) phospholipase C
  • light- rhodopsin: Gtα (transducin): (upregulates) cyclic GMP and phosphodiesterase
  • acetylcholine- M2/M4 muscarinic receptor: Giα, (Gβγ) (downregulates) adenylyl cyclase
  • acetylcholine M1/M3 muscarinic receptor: Gqα, (Gβγ) (upregulates) phospholipase C

Membranes and Receptors (6 decks)

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