- 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

Biological signalling Flashcards by Rebekah Agunede

What are the 2 types of intercellular signalling

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

Signalling between plasma membrane proteins

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What are the three types of signalling by secreted molecules?

Paracrine
Endocrine
Synaptic

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Paracrine signalling

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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Give 2 examples of intracellular receptors

Steroid hormones
Thyroid hormones

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Endocrine

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

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Synaptic signalling

Nerve cell secretes neurotransmitter at synapse to target cell

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What are the subdivisions of signalling molecules

Local chemical mediators
Hormones
Neurotransmitters

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

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What are the 2 types of receptors?

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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What is a receptor?

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

It is functionally silent

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What is a ligand?

Any molecule that binds specifically to a receptor site

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

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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Give 8 roles of receptors

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

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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How are receptors classified?

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

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Acetylcholine receptors: Receptor types and and agonists

Muscarinic (muscarine)

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Muscarinic receptor subtypes and antagonists

M1 - pirenzipine
M2 - Gallamine
M3 - Hexahydrosiladiphenol

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Receptor vs Acceptor

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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Acceptors and modulator - watch lecture

Dihydrofolate reductase - Methotrexate

Sodium channel - Local anaesthetic, neurotoxins

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

Developed transducing protein to form 2nd messenger

Types of signal transduction receptors (4)

Membrane-bound receptors with integral ion channels
Membrane-bound receptors with integral enzyme activity
Membrane-bound receptors which couple to effectors through transducing proteins
Intracellular receptors

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

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

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

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

( nicotinic acetylcholine receptor (nAchR) is an example)

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

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

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

``` 2 domains: Binding domain (extracellular) Catalytic domain (intracellular) ```

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

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)

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

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

Structure of insulin receptor

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

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

Seven transmembrane domain receptors (7TMD)

What are some examples of transducing proteins?

- 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

What is the structure of transducing proteins?

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

How are 7TMD receptors how coupled?

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

What occurs when adrenaline binds to b adrenoreceptors?

activates enzyme adenylyl cyclase increase in cAMP via Gs protein

What happens when acetylcholine binds to M2 muscarinic receptors?

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

Structure of G protein coupled receptor

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

What occurs when ligand binds to G coupled receptor?

GDP is replaced by GTP | a and b subunits disassociate

What do G-proteins do?

- integrate signals - cause amplification

Type of signalling G protein coupled receptors can achieve

Inhibitory response | Stimulatory response

Intracellular receptor structure

Binding domain DNA binding domain (within cell)

How are intracellular receptors activated?

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

Superfamily receptors

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

Amplification in G coupled receptors

1 ligand binding can result in lots of G proteins activated resulting in lots of 2nd messenger production (amplification at each step)

What can cellular activation overall lead to?

Activation or Inhibition eg insulin binds and stimulates glycogen synthesis glucagon stimulates glycogen breakdown to glucose

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

noradrenaline binds to β1 adrenoceptors to increase heart rate