Cell Signalling III

Question 1

What are the types of cell-surface receptor proteins?

Answer 1

Ion-channel coupled receptors

G-protein coupled receptors

Enzyme-coupled receptors

Question 2

What are the typical ion channel coupled receptors?

Answer 2

Transmitter gated ion channels induced by neurotransmitters

Question 3

What is the effect of ion channel coupled receptor binding?

Answer 3

Can either increase or decrease of ion permeability across the membrane

Question 4

Name a common example of a hormone/neurotransmitter that acts on ionotropic receptor in postsynaptic cells:

Answer 4

Acetylcholine

Question 5

How do G protein coupled receptors work?

Answer 5

They indirectly regulate another membrane bound target protein and involve trimeric GTP-binding proteins which interact with the receptor and the effector

Question 6

What are enzyme-coupled receptors?

Answer 6

Receptors with intracellular enzymatic domains that start enzymatic action after binding of ligand to receptor.

Question 7

What are second messengers?

Answer 7

Intracellular molecules that relay signal through the cell after initial binding of first messenger.

Question 8

What kind of molecules can secondary messengers be?

Answer 8

Can be small molecules (GTP, cGMP, cAMP, etc)

Can be water soluble and in the cytoplasm or lipid soluble and capable of diffusing around the plane of the membrane.

Can be proteins (eg SHC, Grb2)

Pass signal through the cell and ultimately binding to and changing effector protein

Question 9

What do effector proteins do?

Answer 9

They are responsible for modifying cell behaviour and can give final response of cell to original signal.

Question 10

What is the purpose of intracellular messengers?

Answer 10

Transforming the signal into a molecular form that can be passed along the pathway to stimulate a response. (creates a practical messenger response)

Allows signal to be relayed from primary site to response production site (transmits signal from one part of the cell to another as needed)

a single extracellular molecule can have a much more pronounced effect on the cell (Amplifies signal to strengthen response)

Signal can be allowed to produce a diverse range of responses to the same signal. (diversifies signal)

Relay signal may be modulated by other factors along the pathway (regulation of signal)

Question 11

What are 2 common modes of intracellular signalling?

Answer 11

GTP binding to replace GDP in response to a signal

Phosphorylation of protein via a protein kinase that is activated by ligand binding

Question 12

How do some bacteria manipulate G protein coupled receptors?

Answer 12

Some bacterial toxins cause disease by altering the activity of G proteins.

Question 13

Describe the structure of a GPCR:

Answer 13

Polypeptide chain traverses membrane as 7-alpha helices

Cytoplasmic portion binds to G protein inside the cell

Receptor structure depends on what molecule will bind to it. small molecules bind deep in the membrane and large proteins require large extracellular domains.

Question 14

What subunits are G proteins composed of?

Answer 14

Alpha

Beta

Gamma

Question 15

How do the G protein subunits attach to the membrane?

Answer 15

Both βγ & α subunit have lipid tails that help attach to membrane

Question 16

What happens when G proteins are activated?

Answer 16

Unstimulated G protein has GDP bound to it. When activated alpha subunit loses affinity for GDP and gains affinity for GTP.

Question 17

How does GPCR activation trigger secondary messenger system?

Answer 17

Activated GPCR activates G proteins – α subunit exchanges
GDP for GTP

Unstimulated state, both receptor and G protein inactive binding extracellular signal molecule to receptor changes
conformation.

Altered conformation of G protein α subunit exchange GDP to GTP

additional conformation change is created resulting in
α and βγ complex dissociating to interact with target proteins

Question 18

What are possible functions of G proteins?

Answer 18

G proteins can interact with ion channels (acetylcholine in heart cells)

G proteins can activate membrane bound enzymes that produce small messenger molecules (adenylyl cyclase or phospholipase)

Question 19

What does adenylyl cyclase do?

Answer 19

Produces cAMP

Question 20

what does phospholipase C do?

Answer 20

Produces inositol triphosphate and diacylglycerol

Question 21

What does inositol triphosphate do?

Answer 21

Promotes accumulation of calcium which is another signalling molecule

Question 22

How does cAMP activate its effects?

Answer 22

It binds to regulatory subunits to release catalytic subunits.

Question 23

How does a rise in intracellular cAMP concentration alter gene transcription?

Answer 23

cAMP activates cyclic-AMP-Dependent Protein Kinase (PKA) which moves to nucleus and phosphorylates transcription factor thus resulting in target gene transcription.

Question 24

How does a rise in intracellular cAMP concentration activate enzymes?

Answer 24

Rise in cAMP activates PKA

PKA phosphorylates and activates enzyme which causes activation of enzyme

Question 25

What is PKA?

Answer 25

Cyclic-AMP-Dependent Protein Kinase (PKA)

Question 26

How does G protein stop acting after being activated? (negative feedback)

Answer 26

G-protein alpha subunit switches itself off by hydrolyzing bound GTP to GDP. Loss of GTP inactivates alpha subunit and so it reassociates with βγ complex

Question 27

How does cholera toxin modify the G protein activation system?

Answer 27

Protein enters cells that line the intestine and modifies alpha subunit of G protein preventing GTP hydrolysis and so G protein is constantly active resulting in excessive outflow of Cl- and water into the gut

Question 28

What other method can GPCRs exert their effects?

Answer 28

Some GPCRs exert effect through G proteins that activate membrane bound enzyme
phospholipase C-β.
Two second messengers are produced from hydrolysis of PI(4,5)P2