cell signalling

Question 1

• What are the 4 reasons we need cell signalling?

Answer 1

To process information

Self-preservation

Voluntary movement

Homeostasis

Question 2

• What direction does an action potential travel?

- How does an action potential travel?

Answer 2

From the pre-synaptic terminal to the post-synaptic cell

Na+ influx and K+ efflux
Via Na+ and K+ transporters

Question 3

• How are neurotransmitters released from vesicles?

- How does the activation of post-synaptic receptors occur?

Answer 3

AP opens voltage gated Ca2+ channels at presynaptic terminal
Ca2+ influx → neurotransmitter vesicle exocytosis into synaptic cleft

NT binds to receptors on post-synaptic membrane
Receptors modulate post-synaptic activity

Question 4

• What is meant by Endocrine Communication?

- Explain what occurs during Hypoglycaemia?

Answer 4

Hormones travel within blood vessels to act on a distant target cell

Glucagon secreted by alpha cells in the islets of Langerhans (in pancreas)
Glucagon travels out of pancreas via blood vessels
Glucagon stimulates glycogenolysis and gluconeogenesis within the liver → increasing blood glucose level

Question 5

• What is meant by Paracrine Communication
• Explain what happens in Hyperglycaemia?
• What other examples?

Answer 5

Hormone acts on an adjacent cell

Increased blood glucose - insulin secretion by beta cells in the Islets of Langerhans
Insulin has paracrine effects: Inhibiting glucagon secretion
Insulin also has endocrine effects on the liver

Nitric oxide on endothelial cells in blood vessels
Osteoclast activating factors from adjacent osteoblasts

Question 6

• What is cell signalling between membrane attached proteins?
• Example of cell signalling between membrane attached proteins? (think immune system)
• What are other examples?

Answer 6

plasma membrane proteins on adjacent cells interacting

Blood borne virus detected within blood stream by antigen presenting cell
    APC digests pathogen and expresses major histo-compatibility (MHC) class II molecules on surface
    Circulating T-Lymphocyte engages with MHC molecule through T-Cell receptor (TCR) interaction

HIV glycoprotein to CD4 receptors on T lymphocytes
Bacterial cell wall components to toll like receptors on haematopoietic cells

Question 7

• What is meant by Autocrine Communication?
• Explain how Autocrine Communication works?
• What are other examples?

Answer 7

Signalling where molecule acts on the same cell

Activated TCR will initiate a cascade of reactions within the 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 cell

growth factor eg TGF beta from tumour cells
AcH to presynaptic M2 muscarinic receptors

Question 8

• What is a ligand?

- What is meant by a second messenger?

Answer 8

A chemical message or molecule that exerts its effects through binding to receptors

Chemical messenger that is a separate entity from receptor or ligand that evokes the intracellular effect

Question 9

• How does the process of ligand-gated channel (ionotropic receptor) activation occur?

Answer 9

Ligand binds to receptor on channel protein

Change in conformation of the channel protein results in the opening of a pore which spans the cell membrane

Pore allows ions to move in or out of the cell according to their respective concentration gradients

Question 10

• What is a G protein complex consisting of?

Answer 10

Alpha subunit

Beta-gamma subunit

Associated GDP molecule

Question 11

• Explain the process involved in G protein complex activation

Answer 11

In resting state, G protein complex is in close proximity to the receptor

Ligand binding causes the G protein complex to associate with the receptor resulting in the GDP molecule being phosphorylated to a GTP molecule

The G-alpha subunit dissociates from the G beta-gamma subunit

Both G-alpha and G beta-gamma can act as secondary messengers

When ligand dissociates from the receptor, internal GTPase on the G-alpha subunit hydrolyses GTP to GDP

G-alpha and G beta-gamma subunits re-associate and are once again available to the receptor

Question 12

• How does enzyme-linked receptor activation occur?

Answer 12

Ligand binding results in receptors clustering

Receptor clustering activates enzyme activity within the cytoplasmic domain

Enzymes phosphorylate the receptor

Phosphorylation leads to binding of signalling proteins to the cytoplasmic domain

These signalling proteins recruit other signalling proteins to the cytoplasmic domain

The signal is terminated when a phosphatase dephosphorylates the receptor

Question 13

• Are steroid hormones membrane permeable?

- What is an intracellular receptor?

Answer 13

Yes, so they can exert their effect on intracellular membranes

A transcription factor, involved in regulation of mRNA and protein synthesis

Question 14

• How do Type I intracellular receptors work?

- Explain how Type II intracellular receptors work?

Answer 14

Located within the cytosolic compartment and are associated with chaperone molecules
Once hormone binds to receptor, hsp dissociates so hormone-receptor complex forms a homodimer with another identical hormone-receptor complex
Homodimer translocates to nucleus where it binds to DNA and acts as a transcription factor

Located within nucleus of the cell and are often already bound to DNA
Binding of hormone ligand to the receptor usually results in direct transcriptional regulation by the activated hormone-receptor complex

Question 15

what are examples of Ligand Gated ion channel receptors

Answer 15

Nicotinic Ach receptors- for Muscle contraction

GABA a receptor- inhibit neuronal activity

NMDA receptor- synaptic plasticity and memory formation

Question 16

What are examples of G protein coupled receptors?

Answer 16

AT-1 Angiotensin II, vasoconstriction, increase BP

M3 muscarinic AcH, bronchi: vasoconstriction, decreased air flow

beta 1 adrenergic adrenaline, increased heart rate and force of contraction

D1 dopaminergic dopamine, increase neuronal growth

M2 muscarinic AcH, decrease heart rate

Question 17

Examples of enzyme linked receptors, their enzyme, ligands and their function?

Answer 17

Insulin (CD220), tyrosine kinase, insulin, glucose uptake

TGF beta R1 , ser/thy kinase, TGF-beta, apoptosis

Question 18

examples of intracellular receptors, their ligands, location and their functions?

Answer 18

GC-R. cortisol, cytosolic, stress, immunosuppression, gluconeogenesis

ER alpha, cytosolic, estradiol, female sexual development

TR alpha, nucleus, thyroxine, growth and inc metabolism