Signalling between Cells II

Question 1

What’s an Ionotropic Receptor?

Answer 1

NAChR - on skeletal muscle at neuromuscular junctions - begins depolarisation –> muscle contraction

GABAa - in CNS, enables transmission of anions, GABA binds to receptor and opens pore –> Cl- influx, depression of activity, blockage –> hyperexcitablity of CNS and epileptic seizures.

Question 2

GPCR

Answer 2

G-protein exists as a heterotrimer.

• Trimer = alpha, beta, gamma subunits
• Beta and Gamma do not dissociate
• GPCR aka serpentine receptors or 7TM receptors

Question 3

How does GPCR work?

Answer 3

• ligand binds and changes receptor conformation
• G-protein heterotrimer binds to internal side of GPCR
• GDP exchanged for GTP
• GTP provides energy for the alpha and beta-gamma subunits.
• subunits go and bind to target proteins
• alpha subunit attaches to the target protein, internal GTPase hydrolyses GTP –> GDP.
• alpha subunit unbidns to target protein and reforms heterotrimer with GDP attached.

Question 4

What are the types of Galpha subunit?

Answer 4

Gs protein linked receptor:

• S = stimulatory
• stimulates adenylyl cyclase
• adenylyl cyclase converts ATP to cAMP
• Increases levels of PKA
• e.g. beta-1-adrenergic receptor

Gi protein linked receptor:

• I = inhibitory
• opposite effect of Gs
• inhibits adenylyl cyclase decreasing cAMP and PKA
• e.g. M2-muscarinic receptor

Gq protein linked receptor:

• activates phospholipase C (PLC)
• PLC converts PIP2 –> IP3 + DAG
• IP3 –> increase in intracellular Ca2+
• DAG - activates PKC
• e.g. AT-1 angiotensin receptor

Question 5

Describe enzyme-linked signal transduction?

Answer 5

• receptors clustered together once the ligand binds –> activation
• receptor clustering activates enzymes in the intracellular compartment
• activation of enzymes –> phosphorylation of the receptor –> binding of signalling proteins to the cytoplasmic domain.
• signalling proteins recruit others and a signal is generated within the cell
• These receptors are linked to Tyrosine Kinase enzymes
• It phosphorylates any protein which has a tyrosine amino acid.
• Signal is terminated when a phosphatase removes the phosphate group.

Question 6

Name the 3 types of Enzyme linked receptor

Answer 6

• Tyrosine Kinase Linked Receptor (95%)
• Guanylyl-cyclase Linked Receptor
• Serine-Threonine Kinase Linked Receptor

Question 7

Describe Intracellular Receptors Type 1

Answer 7

Type 1:

• located in the cytoplasm.
• attached to heat shock proteins.
• ligands usually steroids can pass though the membrane.
• binds to type 1 which dissociates from HSP.
• they move together into the nucleus, binding to DNA and increasing/decreasing transcription.
• these are transcription factors and effects take a while

Question 8

Describe Intracellular Receptors Type 2?

Answer 8

• located in the nucleus and is bound to DNA.

- ligand enters, moves through nuclear envelope and binds to receptor on DNA changing transcription.

Question 9

Examples of Type 1+2 Intracellular Receptors

Answer 9

Type 1 - Glucocorticoid Receptor
Ligand: cortisol, corticosterone
Physiological Effect: Downregulate immune response, increase gluconeogenesis
Agonists: Glucocorticoids

Type 2 - Thyroid Hormone Receptor
Ligand - Thyroxine (T4), Triiodothyronine (T3)
Physiological Effect: Growth and Development
Agonists: Thyroid Hormones