Biological Signalling Receptors

Question 1

What two ways can cells signal?

Answer 1

either by secreted molecules or plasma membrane bound molecules

Question 2

What is plasma membrane bound molecule signalling important for?

Answer 2

in contact inhibition of growth; it prevents over growth of tissue which can lead to cancer

Question 3

What are the three forms of signalling by secreted molecules?

Answer 3

paracrine- signalling molecule releases the signalling cell into the interstitial and the molecule is recognised by target cells within the tissue to produce a response
synaptic- the arrival of an action potential trigger the release of neurotransmitter into the target cell (more complex than this but is an overview)
endocrine- hormone enters the bloodstream after release from the signalling cell and is released from the bloodstream and enters the target cells

Question 4

Local chemical mediators=
Hormones=
Neurotransmitters=

Answer 4

paracrine
endocrine
synaptic
however this classification no longer holds due to the fact some hormones are also neurotransmitters

Question 5

Describe cell surface receptors

Answer 5

the cell surface receptors recognise the hydrophilic signalling molecule, which can’t get inside of the cell, and transduce a message in the cell

Question 6

Describe intracellular receptors

Answer 6

a carrier protein carries the signalling molecule in the blood and releases it at the target tissue, this molecule is a small hydrophobic signalling molecule and so can diffuse directly through the bilayer membrane and bind to the receptor either in the nucleus or the cytoplasm

Question 7

What is a receptor?

Answer 7

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

Question 8

What happens to a receptor in the unbound state?

Answer 8

it is functionally silent

this is when a ligand is not bound to a receptor so there is no signalling in the absence of a signalling molecule

Question 9

What is a ligand?

Answer 9

any molecule that binds specifically to a receptor site

Question 10

What is a ligand agonist?

Answer 10

ligand binding producing activation of the receptor

Question 11

What is a ligand antagonist?

Answer 11

opposes the action of agonist by preventing the binding of the agonist
they do not switch off receptors, they just don’t cause activation of the receptor

Question 12

Give some examples of roles of receptors in cellular physiology

Answer 12

neurotransmission
cellular delivery
cell adhesion
sorting of intracellular proteins
and more...

Question 13

Describe the binding affinity at receptor binding sites

Answer 13

the affinity of ligand binding at receptor sites is generally much higher than binding of substrates and allosteric regulators to enzyme sites

Question 14

Can you explain the reason behind this affinity?

Answer 14

it is because the ligands will be diluted as they are released from the signalling tissue and during the passage to the target tissue therefore they have to have high affinity to be able to see low concentrations of their signal at the recognition tissue

Question 15

How are receptors classified?

Answer 15

according to specific physiological signalling molecule (agonist) recognised

Question 16

How are they then sub-classified?

Answer 16

by affinity of a series of antagonists

Question 17

What is the difference between a receptor and an acceptor?

Answer 17

receptor: silent at rest, agonist binding stimulates a biological response
acceptor: operate in absence of ligand, ligand binding alone produces no response

Question 18

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

Answer 18

1, hydrophilic signal binds to receptor in the membrane
2, signal binds in the membrane causing an ion channel to open
3, transducing molecules in between a receptor coupled to an effector
4, hydrophobic signal enters cell and bind to receptor which then binds to DNA

Question 19

How do the transducing molecules work?

Answer 19

they transduced the signal from the conformational change of a protein through some sort of protein that takes the message onto the effector to produce the second messenger

Question 20

What is the significance of a receptor coupled to an effector?

Answer 20

binding of an agonist to the receptor induces a conformational change which is transmitted to the effector (by the transducing molecules) which then produces the second messenger
this means we could have a number of different sorts of receptor but all activate the same effector so if one receptor became mutated then we still have a family of other receptors that can activate the effector through this mechanism

Question 21

Why are the first two solutions expensive to maintain?

Answer 21

because we need to maintain specificity of receptor sites and specificity of effect or process be it an enzyme or ion channel

Question 22

What are the four different types of signal transduction?

Answer 22

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

Question 23

How have these types been ordered?

Answer 23

by rapidity of response

Question 24

What is the main example for the first type of signal transduction?

Answer 24

ligand gated ion channels

Question 25

What is the structure of one of these channels?

Answer 25

pentameric complex of 5 subunits; 1 gamma, 1 delta, 1 beta and 2 alpha

Question 26

Give three more examples of the classical receptor family

Answer 26

GABA receptor (gamma amino butyric acid)
Glycine receptor
Glutamate receptors (NMDA, AMPA)

Question 27

What is once slightly different membrane bound receptors with integral ion channels?

Answer 27

the IP3 receptor

it is different because it has a different structure- not in the classic pentameric form

Question 28

What happens when the receptors are silent in membrane bound receptors with integral enzyme activity?

Answer 28

the catalytic domains are probably masked by the partner subunit, but on binding of agonists to one or both of the subunits causes a conformational change which is transmitted across each other, so the subunits move against each other and thereby reveal the catalytic domains and activate them on the cytoplasmic side

Question 29

What are examples of these receptors?

Answer 29

ANP receptor, converts GTP to cyclic GMP
Growth factor receptors: insulin, epidermal growth factor, platelet derived growth factor- these are all directly linked to tyrosine kinase

Question 30

How does signalling via tyrosine kinase-linked receptors work?

Answer 30

agonists bind to the receptors, but instead of phosphorylating intracellular targets, the receptor phosphorylates itself on the opposite strand so you get a tyrosine attached to a phosphate group- this process is known as autophosphorylation

Question 31

What is the less common process that can happen next?

Answer 31

the tyrosine phosphates are recognised by specific binding sites on enzymes- they might activate enzymes directly or bring enzyme up to the receptor so the enzyme can be phosphorylated itself on a tyrosine to send off an activated phosphorylated enzyme into the cell

Question 32

What is the more common process that can happen after step 1?

Answer 32

between the receptor and the enzyme there is a transducer molecule- transduced proteins can be phosphorylated by activated receptor, the transducer acts as a docking site for multiple different enzymes to bring those up to the receptor to activate those by enticing phosphorylation

Question 33

What are these transducers?

Answer 33

relatively large proteins, they contain a number of tyrosine phosphorylation sites

Question 34

What is the structure of the insulin receptor?

Answer 34

tetrameric structure- 2 alpha and 2 beta subunits
these are synthesised as one chain during protein biosynthesis and so are a similar pattern to other growth factor receptors

Question 35

What is the difference between insulin and the other growth factor receptors?

Answer 35

post transitionally disulphide links are formed between what will become the alpha and beta subunits and between beta subunits themselves before theres a cleavage within the nascent polypeptide chains to release the alpha subunit from the beta subunit which is held by the disulphide bridge

Question 36

Describe membrane bound receptors that signal through signalling proteins

Answer 36

they are receptors that are coupled through GTP binding regulatory proteins (G proteins) to enzymes or channels
there is additional plasticity within these receptors
they are seven transmembrane domain receptors (7TMD)

Question 37

What is integrated signalling?

Answer 37

where the target enzyme integrates both signals (from inhibitory and stimulatory receptors) and produces a concerted response

Question 38

What happens in the intracellular receptors at rest?

Answer 38

the receptor is prevented from binding to DNA by the binding of inhibitory protein complex

Question 39

What happens when a steroid hormone binds to the receptor?

Answer 39

the receptor undergoes a large conformational change at binding and so dissociates the inhibitory protein complex and reveals the DNA binding site