Receptors

Question 1

What type of receptor are LGICs ?

Answer 1

Ionotropic

Question 2

How quickly do LGICs show a response ?

Answer 2

Within milliseconds

Question 3

Describe the MOA of LGICs ?

Answer 3

1. A ligand binds to the extracellular binding site, causing a conformational change in structure
2. This causes the channel to open
3. The flow of +vely charged ions through the membrane causes depolarisation
4. The flow of -vely charged ions causes hyperpolarisation
5. After depolarisation, a threshold is reached, so voltage gated sodium channels open, sodium ions flow in, which creates an action potential.

Question 4

What is the structure of LGICs ?

Answer 4

They are composed of multiple subunits that form a central pore. Most are:
- Pentameric: 5 subunits (eg. Ach)
- Tetrameric: 4 subunits (eg. Glutamate)
- Trimeric: 3 subunits (eg. P2X)
The Extracellular region has a ligand-binding site.

Question 5

Gs pathway

Answer 5

Activates adenylyl cyclase
cAMP
PKA

Question 6

Gq pathway

Answer 6

Activates PLC
IP3 and DAG
PKC and calcium

Question 7

Gi pathway

Answer 7

Inhibits adenylyl cyclase

Question 8

Describe the MOA of GPCRs ?

Answer 8

A ligand binds to the extracellular region of the receptor, causing a conformational change that activates the receptor.
Upon ligand binding, the Alpha subunit dissociates from the Beta subunit.
These subunits then interact in intracellular signalling pathways: s, q and i.

Question 9

What is the structure of GPCRs ?

Answer 9

1. 7 transmembrane alpha-helical domains, connected by extracellular loops.
2. C-terminal is intracellular- plays a big role in G-protein coupling and regulation of receptor activity.
3. N-terminal is extracellular- involved in post transcriptional modifications.
4. The GPCR is coupled to a protein complex called a G protein, which is composed of alpha, beta and gamma subunits.

Question 10

Describe the structure of KLRs ?

Answer 10

1. Extracellular ligand-binding domain
2. Single transmembrane helix- maintains structure of the receptor
3. Intracellular kinase domain- where kinase activity phosphorylates tyrosine

Question 11

Describe the MOA of KLRs

Answer 11

1. Ligand binds to extracellular domain which causes receptor dimerisation
2. This leads to a conformational change.
3. This activated the kinase and the receptor.
4. Intracellular kinase domain phosphorylates tyrosine residues, which then allows proteins to bind.
5. These proteins activate signalling cascades such as MAPK: RAF to MEK to ERK.

Question 12

What is an examples of a tyrosine receptor?

Answer 12

Epidermal growth factor receptor

Question 13

What is the structure of nuclear receptors?

Answer 13

1. Ligand binding domain
2. DNA-binding domain- enables receptor to bind to specific hormone response elements on DNA.

Question 14

Describe the MOA of nuclear receptors

Answer 14

Class 1
1. Ligand passes across membrane and binds to receptor in cytosol
2. Binding of ligand releases heat shock proteins, which stabilise the receptor
3. Receptor translocates to the nucleus
4. Receptors homodimerise
Class 2
1. Ligand passes across plasma membrane and nuclear membrane and binds to the receptor in the nucleus
2. Binding of the ligand releases repressors
3. Receptor then heterodimerises, which is essential for it to bind to regions of DNA called response elements
4. Receptors bind to hormone response elements which influence transcription via co-activators and co-repressors.