Cell Signalling

Question 1

How does a signal cause a change in a cell?

Answer 1

Signal - receptor - (amplification) transduction - responses

Question 2

What are the 5 types of signals that can be involved in signal transduction?

Answer 2

1. Endocrine signals - released from a gland and travel through the bloodstream to act on a distant target organ e.g insulin
2. Paracrine signals - released from cells to act on adjacent cells
3. Autocrine signals - act on the same cell that they are released from -gh
4. Cell-cell signalling - where the secretory cell is directly attached to the target cell by the signal e.g T cell activation.
5. Ligand - the signals that bind to receptors

Question 3

Describe the lock and key analogy for receptors:

Answer 3

This describes how each hormone has its own specific receptor. Only when the hormones or ligand engages with the correct receptor can it activate the receptor and trigger intracellular signalling leading to a response

Question 4

How do drugs inhibit the receptor?

Answer 4

They can either partially block the receptor by not properly fitting into it or they can mimic its effect to inhibit intracellular signalling

Question 5

Why does the receptor undergoes a conformational change when a hormone/ligand binds to it:

Answer 5

This is done so that signalling can occur without a hormone passing through the membrane allowing the receptor to act as a gate keeper or activity so that activity can be controlled at the cell surface

Question 6

Describe the process of transduction:

Answer 6

The arrival of the signal then needs to be relayed through the cell - transduced. Cascades of molecular interactions relay signals from the receptors to target molecules in the cell. It usually involves multiple steps which can amplify a signal. It provides more opportuities for coordination and and regulation of cellular responses.

Question 7

What are the 2 most common methods of signal transduction?

Answer 7

1. Second messengers

2. Phosphorylation

Question 8

Describe how second messengers work:

Answer 8

They are chemical signals that are not embedded in the membrane that can diffuse in and out of the cell to pass on the message. They change in concentration to convey info to the cell. And example of this is cAMP which can occur in many tissues and cells because other aspects are tissue specific

Question 9

How does the same signal have different effects in different cells?

Answer 9

Because different types of cells have different collections of proteins which allow cells to detect and respond to different signals. Each cell has different proteins and pathways. Pathway branching and cross-talking further helps the cell to coordinate incoming signals

Question 10

How does phosphorylation occur and what is it?

Answer 10

Phosphorylation and dephosphorylation act as a molecular switch that can turn protein activity up/down or on/off as required by the cell. Protein kinases transfer phosphates from ATP to protein. Many relay molecules in signal transduction pathways are protein kinases creating a cascade. Protein phosphotases do dephosphorylation

Question 11

Describe signal amplification:

Answer 11

At each step the number of activated products is much greater than the preceding step. This means that only a very small amount of the initial hormone is required and a few receptors need to be activated to produce a response i.e each receptor may produce many second messenger molecules to amplify the signal

Question 12

Describe the cellular response

Answer 12

The changes in chemicals result in the activation or inhibition of proteins e.g pumps enzymes etc

Question 13

Describe the termination step of signal transduction:

Answer 13

After the cell has completed its response to a signal the process must be terminated so that the cell can respond to new signals. Signalling processes that fail to terminate can have highly undesirable consquences

Question 14

Name and describe the 3 receptor classes:

Answer 14

1. G protein coupled receptors GPCR’s - receptors that work with the help of a G protein
2. Receptor tyrosine kinases RTK - receptors that attach phosphates to tyrosines to signal
3. Ligand gated ion channel receptors - a signal molecule binds as a ligand to the receptor, opening the receptor gate and allowing specific ions to pass through a channel in the receptor into the cell

Question 15

Describe the structural features of a GPCR:

Answer 15

7 transmembrane regions (serpintine) - with an extracellular N-terminus and intracellular C-terminus. There are 3 intracellular loops and 3 extracellular loops

Question 16

Describe a simple GPCR signal transduction:

Answer 16

The binding of the hormone to its specific GPCR which spans the membrane results in a change in the structure of the protein and the activation of intracellular proteins (G-proteins). The G protein then interacts with adenylate cyclase which converts ATP into cAMP a second messenger molecule. This chemical activates protein kinase A (PKA) which is capable of phosphorylating many different proteins.

Question 17

Describe the G proteins cycle:

Answer 17

The cycle starts with the inactive receptor and the inactive G protein in its GDP bound trimer state. The GPCR is activated by a hormone that causes a conformational change in the receptor that allows an interaction between the receptor and G protein to occur. The activated receptor then binds to the G protein via the a subunit. This interaction induces a conformational change in the a subunit which opens up the nucleotide binding site so that GDP can depart and GTP can take its place. At the same time, the a subunit dissociates from the by subunit. This dissociation allows transmission of the signal that the receptor has bound to a ligand. The a subunit interacts and activates a downstream effector protein. A single activated receptor can stimulate nucleotide exchange in many G proteins resulting in an amplified response. The effector then propagates the signal. The a subunit of the G protein has built in “intrinsic” GTP ase activity which hydrolyses deactivation of the a subunit. The bound GTP is like a clock that resets the alpha subunit after a certain period of time. The GDP form of a G protein can then reassociate with the by subunit to return back to the heterotrimeric protein.

Question 18

Name and describe the 3 types of G proteins:

Answer 18

1. Gs = stimulatory G protein that activates adenylate cyclase
2. Gi = inhibitory G protein that inactivates adenylate cyclase
3. Gq = activates a different receptor - phospholipate C

Question 19

Describe how glucagon signalling occurs:

Answer 19

Glucagon is released from the islets of langerhans in the pancreas and they circulate in the blood to get to the liver where they bind to its specific receptor - the glucagon receptor. When blood sugar levels are low, these events are triggered ensuring energy availabilty

Question 20

Describe epinephrine signalling:

Answer 20

It is released from the adrenal glands in the kidneys and circulates in the blood to go to the muscle tissues where it binds to its specific receptor - the epinephrine receptor. It is released during a fight or flight response.

Question 21

What are 4 ways that the glycogen breakdown can be turned off?

Answer 21

1. The hormones that stimulate glycogen breakdown are no longer present
2. The inherent GTPase activity of the a subunit of the G protein inactivates G protein signalling
3. Phosphodiesterase converts cAMP into AMP which does not stimulate protein kinase A
4. A protein phosphatase removes phosphates from phosphorylase kinase and glycogen phosphorylase thereby inactiaving the enzymes

Question 22

What is vision based on and describe the structure of the photoreceptors?

Answer 22

The absorption of photons (light) in the photoreceptor cells (rod and cones) in the eye. The photoreceptor molecules in rods is rhodopsin which is made of the protein opsin and a prothetic group 11-cis-retinal which is a light absorbing group (chromophore)

Question 23

Describe the receptor signalling of rhodopsin:

Answer 23

When light is absorbed in the rods, it induces a specific isomerisation of the bound 11-cis-retinal to form all-trans-retinal (metarhodopsin). This form of rhodopsin activates the G protein transducin which interacts with the enzyme phosphodiesterase (by removing an inhibiting subunit) which converts cGMP to GMP. The reduction in cGMP concentration causes cGMP gated ion channels to close, leading to the hyperpolarization of the membrane and neuronal signalling to the brain

Question 24

Describe the function of the cones in the eye:

Answer 24

These are for colour vision and they are mediated by 3 cone receptors which are homologues of rhodopsin. In humans there are 3 distinct photoreceptor proteins with absorption maximas at 426, 530 and 560 nm

Question 25

How is colour blindness caused?

Answer 25

By an x-linked autosomal recessive mutation in the cone opsins

Question 26

How is retinitis pigmentosa caused and what does it affect?

Answer 26

By an autosomal dominant recessive mutation in the rhodopsin. This disease causes loss of sight in peripheral and night vision before causing complete blindness

Question 27

How do drugs inhibit signals?

Answer 27

They bind to the active site in place of the native molecule and either block the signal or mimic its effects

Question 28

Describe how B2 adrenoreceptor agonists work for the treatment of asthma:

Answer 28

It has a similar structure to epinephrine and binds to a GPCR etc etc then a protein kinase A which phosphorylates myosin light chain kinase that cause smooth muscle relaxation.

Question 29

What is an example of a receptor tyrosine kinase?

Answer 29

Insulin

Question 30

Describe the insulin receptor tyrosine kinase and how it works:

Answer 30

it is a dimer of 2 monomers (a and B bound by a disulfide bond) where the B subunit spans the membrane and the a sits outside. when insulin binds it triggers a conformational change ad leads to autophosphorylation of tyrosine residues