Cell Signalling

Question 1

2 main systems within the body that produce lines of communication

Answer 1

Blood systems and nerves

Question 2

Why do cells need to communicate

Answer 2

Homeostasis, process information, self preservation ,voluntary movement

Question 3

Step 1 of neurotransmission

Answer 3

1. Propagation of the action potential (AP)
   • AP is propagated by VGSCs opening
   • Na+ influx ® membrane depolarisation ® AP ‘moves along’ neurone
   • VGKC opening ® K+ efflux ® Repolarisation

Question 4

Step 2 of neutransmission

Answer 4

2. Neurotransmitter (NT) release from vesicles
   • AP opens voltage-gated Ca2+ channels at presynaptic terminal
   • Ca2+ influx ® vesicle exocytosis

Question 5

Step 3 of neurotransmission

Answer 5

3. Activation of postsynaptic receptors
   • NT binds to receptors on post-synaptic membrane
   • Receptors modulate post-synaptic activity

Question 6

Step 4 of neurotransmission

Answer 6

4. Activation of postsynaptic receptors

• The signal can be transmitted by a variety of different types of receptor

Question 7

What is endocrine communication

Answer 7

Hormones which travel by blood vessels to target organs/distant target cells

Question 8

What is paracrine communication

Answer 8

Acting on a cell next to it - eg insulin acting on alpha cells that release glucagon in the pancreas during hyperglycaemia, - Nitric Oxide produced by endothelial cells in blood vessels fro vasodilation when people go into septic shock
- Osteoclast activating factors produced by adjacent osteoblasts(bone formation)

Question 9

Signalling between membrane attached proteins

Answer 9

1. Blood borne virus (e.g. Hepatitis C) ® detected within blood stream by antigen presenting cell (APC)
2. APC digests pathogen ® expresses major histo-compatibility (MHC) class II molecules on surface
3. Circulating T-lymphocyte engages with MHC molecule through T-cell receptor (TCR) interaction

Other examples: Covid 19 and ACE 2 , 1. HIV GP120 glycoprotein ® CD4 receptors on T-lymphocytes, Bacterial cell wall components ® toll-like receptors on haematopoietic cells

Question 10

Autocrine signalling

Answer 10

Acts on the same cell.
• Activated TCR will initiate a cascade of reactions within T-cell
• Activated T-cell expresses interleukin-2 (IL-2) receptor on surface
• Activated T-lymphocyte also secretes IL-2, which:
• Binds to IL-2 receptor on same cell
• Binds to IL-2 receptor on adjacent activated T-cell ( paracrine)

Other examples:

1. Acetylcholine ® presynaptic M2- muscarinic receptors
2. Growth factors (e.g. TGFb) from tumour cells ® mitogenesis

Question 11

4 types of receptors

Answer 11

Intracellular, enzyme linked, ionotropic ,G protein coupled

Question 12

How does an ionotropic receptor work

Answer 12

Ionotropic Receptors

Signal transduction events

1. Ligand binds to the receptor protein
2. Change in conformation of channel protein ® opening of a pore
3. Pore allows ions to move in or out of cell according to their respective concentration gradients

Question 13

Example of ionotropic receptor

Answer 13

Ionotropic receptor example
Nicotinic Acetylcholine 
Ligand: Acetylcholine (ACh)
Location: Skeletal muscle
Physiological effect: Muscle contraction

GABA: inhibition of neural activity
NMDA; glutamate and synaptic plasticity and memory formation
5-HT3 receptor ligand 5HT has anxiety and emetics effects

Question 14

How do G- protein coupled receptors work

Answer 14

The process involved in G protein activation is summarised below in a step-wise process:

1. In the resting state the G protein complex consists of a Gα subunit, a Gβγ subunit and an associated GDP molecule, which are in close proximity to the receptor
2. Ligand binding causes the G protein complex to associate with the receptor resulting in the GDP molecule being phosphorylated to a GTP molecule
3. The Gα subunit dissociates from the Gβγ subunit. Ga and GTP are now together and bind to target protein
4. Both Gα and Gβγ can act as second messengers
5. 5. Internal GTPase activity on a-subunit dephosphorylates GTP ® GDP
6. a-subunit dissociates from target protein ® inactive again
7. The Gα and Gβγ subunits re-associate and are once again available to the receptor

Question 15

How do enzyme linked disorders work

Answer 15

1. Ligand binding ® receptors clustering
2. Receptor clustering activates enzyme activity within cytoplasmic domain
3. Enzymes phosphorylate receptor
4. Phosphorylation ® binding of signalling proteins to cytoplasmic domain
5. These signalling proteins ® recruit other signalling proteins ® signal is generated within cell
   Normally utilised tyrosine kinase enzymes.

Examples insulin/ tyrosine kinase

Question 16

How do cytoplasmic intracellular proteins work

Answer 16

Type 1 - Cytoplasmic

1. Located within the cytosolic compartment 
2. Associated with chaperone molecules (heat shock proteins, hsp)  
3. Hormone binds to receptor ® hsp dissociates 
4. 2 hormone bound receptors form a homodimer. 
5. The homodimer translocates to the nucleus ® binds to DNA 

Example: Type 1 - Glucocorticoid receptor
Ligands: Cortisol, corticosterone
Physiological effect: ¯ immune response, ­Gluconeogenesis

Question 17

How do nuclear intracellular receptors work

Answer 17

Type 2 - Nuclear

1. Located within the nucleus 
2. Binding of hormone ligand ® transcriptional regulation

Example : Type 2 - Thyroid hormone receptor
Ligand: Thyroxine (T4), triiodothyronine (T3)
Physiological effect: Growth &development

Question 18

What is a ligand

Answer 18

Chemical messages or molecules which exert effects through binding to receptors

Question 19

What is a receptor

Answer 19

Proteins that bind the chemical mediators known as ligand and upon activation they elicit an effect within a cell

Question 20

What is a second messenger

Answer 20

The chemical messenger that provokes the intracellular effect after a ligand binds to a receptor

Question 21

Examples of G protein coupled receptors

Answer 21

AT 1 - Gaq subunit
M3 muscarinic -Gaq subunit
M2 muscarinic -Gai subunit 
B1 adrenergic -Gas subunit
D1 dopaminergic -Gas subunit
A2 adrenergic - Gai subunit

Question 22

Examples of enzyme linked receptors

Answer 22

ErbB receptor
Insulin
NPR1
TGF Beta R1