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ICPP 2023 > Biological signalling > Flashcards

Biological signalling Flashcards

1
Q

What are the 2 types of intercellular signalling

A
  • Signalling by secreted molecules to receptor on target cell
  • Signalling by plasma membrane-bound molecules

Signalling between plasma membrane proteins

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2
Q

What are the three types of signalling by secreted molecules?

A
  • Paracrine
  • Endocrine
  • Synaptic
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3
Q

Paracrine signalling

A
  • The signalling between cells within a tissue
  • A local mediator is released by a cell and is received by an adjacent cell within the tissue
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4
Q

Give 2 examples of intracellular receptors

A
  • Steroid hormones
  • Thyroid hormones
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5
Q

Endocrine

A

Hormone produced by gland travels through blood to act on distant target cell

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6
Q

Synaptic signalling

A

Nerve cell secretes neurotransmitter at synapse to target cell

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7
Q

What are the subdivisions of signalling molecules

A
  • Local chemical mediators
  • Hormones
  • Neurotransmitters

Note: this classification, while still useful, no longer holds

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8
Q

What are the 2 types of receptors?

A
  • Cell surface receptors (hydrophilic molecules can’t cross membrane, transported in blood via carrier)
  • Intracellular receptors (small hydrophobic molecules can cross)
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9
Q

What is a receptor?

A

A receptor is a molecule that recognises specifically a second molecule (ligand) or family of molecules and which in response to ligand binding brings about regulation of a cellular process

response to ligand binding brings about regulation of cellular process

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10
Q

How do you describe a receptor in it’s unbound state?

A

It is functionally silent

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11
Q

What is a ligand?

A

Any molecule that binds specifically to a receptor site

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12
Q

What are the 2 types of ligand?
What does each one do?

A

1) Agonist
2) Antagonist

An agonist = binds to activate a receptor
An antagonist = binds but doesn’t activate the receptor (prevents agonist binding)

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13
Q

Give 8 roles of receptors

A
  • Signalling by hormones/local chemical mediators
  • Neurotransmission
  • Cellular delivery
  • Control of gene expression
  • Celladhesion
  • Modulation of the immune response
  • Sortingofintracellularproteins
  • Release of intracellular calcium stores
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14
Q

What is the binding affinity of receptors like?
Compared to what?

A

Ligand - very high affinity (Kd)
Compared to the binding of substrates and allosteric regulators to enzyme sites (Km)

Enzyme - lower (Km)

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15
Q

How are receptors classified?

A 
Specific Agonist recognised (eg Ach receptor)
Sub-classified by affinity for antagonists (eg nAchR)
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16
Q

Acetylcholine receptors: Receptor types and and agonists

A

Muscarinic (muscarine)

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17
Q

Muscarinic receptor subtypes and antagonists

A

M1 - pirenzipine
M2 - Gallamine
M3 - Hexahydrosiladiphenol

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18
Q

Receptor vs Acceptor

A
  • Receptors are silent at rest (no activity)
  • Agonist binding stimulates a biological response
  • Acceptors operate in absence of a ligand (need ligand binding and something else)
  • Ligand binding alone produces no response
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19
Q

Acceptors and modulator - watch lecture

A

Dihydrofolate reductase - Methotrexate

Sodium channel - Local anaesthetic, neurotoxins

20
Q

How has evolution solved the problem of transducing extracellular into intracellular signals? - watch lecture

A

Developed transducing protein to form 2nd messenger

21
Q

Types of signal transduction receptors (4)

A
  1. Membrane-bound receptors with integral ion channels
  2. Membrane-bound receptors with integral enzyme activity
  3. Membrane-bound receptors which couple to effectors through transducing proteins
  4. Intracellular receptors
22
Q

What are the 5 methods of tranducing extracellular into intracellular signals?

A

-Receptor has intracellular enzyme
-Recpetor opens channel
-Receptor coupled to effector
-Receptor coupled to transducing molecule
-Hydrophobic signal to intracellular receptor

23
Q

Describe the structure of a classic receptor family and give an example

A 
5 subunits (2a, b, gamma and delta)
The subunits make a pore
Closed pore when silent

( nicotinic acetylcholine receptor (nAchR) is an example)

24
Q

Name 3 Membrane bound receptors with a classic receptor family with integral ion channels and state the receptor and the ion selectivity

A
25
Q

Name 1 Membrane bound receptors with a classic receptor family with integral ion channels and state the receptor and the ion selectivity

A
26
Q

What is the structure of an MBR with integral enzyme activity?

A 
2 domains:
Binding domain (extracellular)
Catalytic domain (intracellular)
27
Q

1) What are some examples of Membrane Bound Receptors with integral enzyme activity?
2) Describe their integral enzyme activity
3) Give examples

A

1) - ANP (atrial natruiretic peptide) receptor
2) linked directly to guanylyl cyclase
3) GTP –> cGMP

1) Growth factor receptors
2) linked directly to tyrosine kinase
3) Insulin, epidermal growth factor (EGF) platelet-derived growth factor (PDGF)

28
Q

How does signalling occur via tyrosine kinase linked receptors? - watch lecture

A
  • Agonist binds to tyrosine causing autophosphorylation
  • Tyrosine kinase activates enzymes (via direct phosphorylation)
  • or transducing proteins (transducers recognise phosphorylated tyrosine)
29
Q

Structure of insulin receptor

A

Insulin binding domain (extracellular)
Transmembrane domain in the plasma membrane
Tyrosine kinase domain (inside)

Tyrosine kinase domain (inside)

30
Q

What are membrane bound receptors that signal through transducing proteins known as?

A

Seven transmembrane domain receptors (7TMD)

31
Q

What are some examples of transducing proteins?

A
  • Adrenaline binds to β-adrenoceptors which activates ATP cAMP via the G-protein Gs

-ACh binds to M2 muscarinic ACh receptors wihich stimulates K+ channel opening via the G-protein Gi

32
Q

What is the structure of transducing proteins?

A

7 transmembrane domains
-coupled through G proteins to enzymes of channels
-folded structure-lignad binds in pore

33
Q

How are 7TMD receptors how coupled?

A

Coupled through GTP-binding regulatory proteins (G-proteins) to enzymes or channels

34
Q

What occurs when adrenaline binds to b adrenoreceptors?

A

activates enzyme adenylyl cyclase
increase in cAMP
via Gs protein

35
Q

What happens when acetylcholine binds to M2 muscarinic receptors?

A

Stimulates K+ channel opening via Gi protein (suppress electrical activity)

via Gi protein

36
Q

Structure of G protein coupled receptor

A

Binding domains: extracellular or within membrane
G coupled protein domains within cell
Form cleft around ligand

37
Q

What occurs when ligand binds to G coupled receptor?

A

GDP is replaced by GTP

a and b subunits disassociate

38
Q

What do G-proteins do?

A
  • integrate signals
  • cause amplification
39
Q

Type of signalling G protein coupled receptors can achieve

A

Inhibitory response

Stimulatory response

40
Q

Intracellular receptor structure

A

Binding domain
DNA binding domain

(within cell)

41
Q

How are intracellular receptors activated?

A

Inhibitory protein complex covers DNA binding site on receptor
Hormone binds to binding site
Conformational change = Inhibitory protein removed
DNA binding site exposed
= alter transcription

42
Q

Superfamily receptors

A

Intracellular = steroid and thyroid (have homology/similar structure)

43
Q

Amplification in G coupled receptors

A

1 ligand binding can result in lots of G proteins activated
resulting in lots of 2nd messenger production

(amplification at each step)

44
Q

What can cellular activation overall lead to?

A

Activation or Inhibition

eg insulin binds and stimulates glycogen synthesis
glucagon stimulates glycogen breakdown to glucose

45
Q

In cardiac pacemaker cells, noradrenaline binds to … to … heart rate

A

noradrenaline binds to β1 adrenoceptors to increase heart rate

ICPP 2023 (31 decks)

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