Cell Signalling

Question 1

Why do cells need to communicate?

Answer 1

1. Process information: sensory stimuli (e.g. sight and sound)
2. Self preservation: identify danger and take appropriate action, spinal reflexes, sympathetic nervous system
3. Voluntary movement: getting A to B, completing daily tasks
4. Homeostasis: thermoregulation, glucose homeostasis

Question 2

What is endocrine communication in hypoglycaemia like?

Answer 2

• Physiological response: glycogen breakdown (glycogenolysis), gluconeogenesis
• Process:
  1. Glucagon: secreted by alpha cells of islets of Lagerhands
  2. Glucagon travels out of of pancreases in blood vessels
  3. Glucagon stimulates glucogenolysis and gluconeogenesis within the liver increasing blood sugar levels

Question 3

What is another example of endocrine signalling?

Answer 3

-Hormone travels within blood vessels and acts on distant target cells
E.g. adrenaline produced in adrenal glands to trachea, insulin in pancreas acts on liver, muscle cells and adipose tissue

Question 4

What is paracrine communication in hypoglycaemia like?

Answer 4

• Physiological response: Glucose uptake, Reduced glycogenolysis, Reduced gluconeogenesis
• Process:
  1. Increased blood glucose - insulin secretion by b- cells in the Islets of Langerhans
  2. Insulin has paracrine effects:
  3. Inhibiting glucagon secretion
  4. Insulin also has endocrine effects on the liver

Question 5

What is another example of paracrine signalling?

Answer 5

Paracrine signalling
-Hormone acts on adjacent cells
E.g. nitric oxide produced by endothelial cells in blood vessels, osteroclast activating factors produced by adjacent osteoblasts

Question 6

What is signalling between membrane attached proteins like?

Answer 6

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
-Plasma membrane proteins on adjacent cells interacting
E.g. HIV GP12- glycoprotein to CD4 receptors on T lymphocytes, bacterial cell wall components to toll-like receptors on haematopoietic cells

Question 7

What is the process and some example of autocrine communication?

Answer 7

-Autocrine signalling:
1. Activated TCR will initiate cascade of reactions within T cell
2. Activated T cell expresses interleukin-2 (IL-2) receptor on surface
3. 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
4. Signalling molecule acts on same cell
E.g acetylcholine to presynaptic M2-muscarinic recptors, growth factors (e.g. TGFbeta) from tumour cells to mitogenesis

Question 8

What is the process of neurotransmission?

Answer 8

1. Propagation of action potential (AP):
   - AP is propagated by VGSCs opening
   - Na+ influx - membrane depolarisation - AP ‘moves along’ nuerone
   - VGKC opening - K+ efflux - repolarisation
2. Neurotransmitter (NT) release from vesicles
   - AP opens voltage gated Ca2+ channels at presynaptic terminal
   - Ca2+ influx - vesicle exocytosis
3. Activation of postsynaptic receptors:
   - NT binds to receptors on post-synaptic membrane
   - Receptors modulate post-synaptic activity
4. Activation of postsynaptic receptors
   - The signal can be transmitted by variety of different types of receptor

Question 9

What are different types of receptor?

Answer 9

1. Ionotropic receptor: ligand binding -> opens ion permeable pore traversing the membrane
2. . G protein couple receptor: ligand binding -> activates intracellular G-protein
3. Enzyme linked receptor: ligand binding -> receptor clustering -> activates internal enzymes
4. Intracellular receptor: a membrane permeable ligand binds to receptor inside cell.

Question 10

Describe ionotropic receptor and give an example

Answer 10

Signal transduction events:
1. Ligand binds to receptor protein 
2. Change in conformation of channel protein -> opening of a pore
3. Pore allows ions to move ion or out of cells according to conc gradients 
E.G Nicotinic Acetylcholine
Ligand: Acetylcholine (ACh)
Location: Skeletal muscle 
Physiological effect: muscle contraction

Question 11

Describe G-protein coupled receptors

Answer 11

Signal transduction events

1. 7-TM receptor and heterotrimeric G-protein are inactive
2. Ligand binding -> changes confrontation of receptor
3. Unassociated G-protein binds to the receptor -? Bound GDP molecule is phosphorylated to GTP and GDP exchanged for GTP
4. G-protein dissociates into two active components: alpha subunit and Betagamma subunit and bind to their target proteins
5. Internal GTPase activity on alpha subunit dephosphorylase GTP -> GDP
6. Alpha subunits dissociates from target protein -> inactive again
7. Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins

Question 12

What are the different types of G protein and examples?

Answer 12

1. Gs protein linked receptor: stimulates adenylyl cyclase:
   -Converts ATP to cAMP
   -cAMP activate PKA
   E.g. beta 1 adrenergic receptor
2. Gi protein linked receptor: inhibits adnyilyl cyclase
   -Reduces levels of PKA
   E.g. M2-muscarinic receptor
3. Gq protein linked receptor: stimulates PLC
   -Cinverts PIP2 to IP3 and DAG
   -IP3 stimulates Ca2+ release
   -DAG activates PKC
   E.g. AT-1 angiotensin receptor

Question 13

What are enzyme linked receptors?

Answer 13

1. Ligand binding -» receptors clustering
2. Receptor clustering activates enzyme activity within cytoplasmic domain
3. Enzyme phosphorylase receptor
   Phosphorylation -» binding of signalling proteins to cytoplasmic domain
   4.These signalling proteins —> recruit other signalling proteins -» single is generated within cell

Question 14

What are examples of enzyme linked receptors?

Answer 14

1. Insulin receptor (CD220 antigen)
   Ligand: insulin
   Physiological effect: glucose uptake
2. ErbB receptors
   Ligand: Epidermal Growth Factor, transforming growth factor beta
   Physiological effect: Cell growth, proliferation

Question 15

What are Type 1 intracellular receptors?

Answer 15

Type 1 - Cytoplasmic
1. Located in cytosolic compartment
2. Associated with chaperone molecules (heat shock proteins, hsp)
3. Hormone binds to receptor -> hip dissociates
2 hormone bound receptor form a homodimer
4. Homodimer translates to nucleus —> binds to DNA

Question 16

What is an example of Type 1 intracellular receptor?

Answer 16

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

Question 17

What are of Type 2 intracellular receptors?

Answer 17

Type 2 - Nuclear

1. Located within nucleus
2. Binding of homorne ligand -> transcriptional regulation

Question 18

What is an example of Type 2 intracellular receptor?

Answer 18

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