MnR S7 - Signal transduction in biological membranes

Question 1

Name two diseases associated with GPCR mutations that result in loss of function and the receptor effected

Answer 1

Retinitis pigmentosa - Mutation to rhodopsin

Nephrogenic diabetes insipidus - Mutation to V2 vasopressin receptor

Question 2

What is familial male precocious puberty caused by and how does it differ from retinitis pigmentosa and nephrogenic diabetes insipidus?

Answer 2

Mutation to the luteinizing hormone receptor so can act independently of ligand binding

Results in gain of function as opposed to loss of function

Question 3

Outline the general structure of a G-protein

Answer 3

Heterotrimeric protein made up of alpha, beta and gamma subunits

Question 4

How does activation of G-proteins by binding to activated GPCRs results in cellular response?

Answer 4

• GDP bound to alpha subunit is exchanged for a GTP
• Stimulates dissociation of alpha subunit from beta-gamma subunit
• Each subunit is then free to interact with effector molecules

Question 5

How isi G-protein activity terminated?

Answer 5

• Interaction with effector molecules lasts till alpha subunit GTPase hydrolyses the GTP molecule back to GDP
• Alpha and beta-gamma subunits then recombine to form inactive heterotrimeric complex

Question 6

How is it possible that there are over 1000 G-alpha-beta-gamma combinations of g protein?

Answer 6

20 different G alpha subunits, 5 different G beta subunits and 12 different G gamma subunits that combine in different combinations

Question 7

Outline how adenylyl cyclase cyclase can be activated as an effector of G proteins

Answer 7

• Agonist binds to GPCR
• G-alpha s subunit is activated
• Binds to adenylyl cyclase and increases production of cAMP

Question 8

What effect does the cAMP produced have?

Answer 8

Activates PKA causing release of the catalytic subunits which phosphorylate target proteins

Question 9

What subunit of the activated G protein interacts with phospholipase C and what effect does this have?

Answer 9

• G alpha q binds to phospholipase C
• Stimulates cleavage of PIP3 into IP3 and DAG
• IP3 binds to receptors on SR/ER causing calcium ion release
• DAG binds to PKC

Question 10

Outline the signalling pathway that occurs signalling pathway that occurs when sympathetic noradrenaline binds to beta-1 adrenoceptors to cause increased isotropy in the heart

Answer 10

• Activates G-alpha s subunit
• Binds to adenylyl cyclase
• Increases cAMP production
• Activates PKA
• Stimulates inflow of Ca2+ via VOCC which increases contractility

Question 11

Outline the signalling pathway involved in increasing smooth muscle contraction, stimulated by the binding of noradrenaline to alpha-1 adrenoceptors

Answer 11

• Activated G-alpha q subunit
• Stimulates phospholipase C
• Cleaves PIP2 into IP3 and DAG
• Opens calcium ion channels

Question 12

Name a neurotransmitter other than noradrenaline that activates the G alpha q pathway, the receptor it binds to and its general effect

Answer 12

• Acetylcholine
• M3 receptors
• Bronchoconstriction

Question 13

How does the signalling pathway pathway involved in modulation of neurotransmitter release differ from those involved in increasing inotropy in the heart and smooth muscle contraction?

Answer 13

• Morphine is the ligand involved
• Binds to mew-opioid receptors
• Beta-gamma subunit stimulates the effector opposed the alpha subunit