Session 6 ILOs - Biological signalling and Receptors

Question 1

Discuss the principals of communication between cells via chemical messengers in the paracrine systems, endocrine systems and in the nervous systems

Answer 1

Paracrine - where the signalling molecule (local chemical mediator) is released into the interstitial space which is recognised by the target cells within the tissue = produce a response
Endocrine - where the hormone is released into the blood stream where the hormone is recognised by the target tissue as a distant site
Synaptic - where neurotransmitters are released from the pre-synaptic membrane and recognised by receptors on the post-synaptic membrane

Question 2

Describe the role of receptors in transfusing the information carried by an extracellular hydrophilic signalling molecule across a hydrophobic cellular membrane bilayer

Answer 2

Hydrophilic signals can be carried across the lipid membrane by binding to the receptor to cause a conformational change, leading to activation of an enzyme/effector which converts the substrate into a second messenger or through an ion channel.

However, G-proteins are the better solution where binding causes a conformational change which is transmitted to the effector, which then produces the second messenger

Question 3

Explain the concept of receptor super-families, based on common structural motifs

Answer 3

The receptors consist of subunits, each having 4 transmembrane domains, which form complexes of varying elements - all integral ion channels
EXAMPLES: Classical receptor families
nAChR & Glutamate receptors (cation channels - depolarising response)
GABA & Glycine (Cl- channels - hyperpolarising response)

Question 4

Describe the mechanisms employed by the 4 major classes of receptors involved in cellular signalling via hormones, local mediators and neurotransmitters

Answer 4

Kinase-linked - Where binding of a hydrophilic signal leads to autophosphorylation (phosphorylates itself on the opposite strand), the phosphorylated tyrosine is recognised by the transducer which acts as a docking site for multiple different enzymes which can then activate an enzyme to convert a substrate to a second messenger
EXAMPLE: Growth factor receptors e.g. insulin

Ligand gated (I)on channels - Where binding of a hydrophilic signal to the alpha subunits of the pentomeric receptor leads to the opening of an ion channel and the influx of an ion which changes the membrane potential e.g. depolarisation 
EXAMPLE: Nicotinic Ach Receptors

Nuclear / Intracellular - where a hydrophobic signal is able to cross the membrane - on binding of a hormone, the inhibitory protein complex is displaced (due to conformational change by the receptor) and exposes the DNA binding site to be exposed. This can then affect transcription
EXAMPLE: Oestrogen receptor

G-protein receptor - On binding of a adrenaline, the GDP dissociates and is replaced by a GTP to form a Gs-alpha GTP complex - this actives an enzyme to convert ATP to cAMP which is a second messenger
EXAMPLE: Adrenaline binding to Gs protein