Signal Transduction

Question 1

What are the 3 stages of cell signalling?

Answer 1

Reception, transduction and response

Question 2

What are the 3 origins of cell signals?

Answer 2

Paracrine, autocrine and endocrine

Question 3

What does paracrine signalling involve?

Answer 3

Chemicals released by cells have action upon neighbouring populations of different cells. Movement through diffusion.

Question 4

What does autocrine signalling invovle?

Answer 4

Chemicals released by cells have action upon the same population of same type cells or the cell that released the signal.

Question 5

What does endocrine signalling involve?

Answer 5

Chemical signal travels through the bloodstream and acts on distant populations of target cells.

Question 6

What are the 3 types of cell surface membrane receptors?

Answer 6

G protein-coupled receptors, ligand-gated ion channels and catalytic receptors

Question 7

When is a signal detected?

Answer 7

When the chemical signal (ligand) binds to a receptor protein on the surface of a cell or inside the cell.

Question 8

What is a conformational change?

Answer 8

Ligands transmit information to the cell by inducing this change which changes the shape of the receptor. This change allows other proteins to interact with the receptor, setting off a signalling cascade.

Question 9

What is the process of transduction?

Answer 9

The neurotransmitter activates the GPCR –> the GPCR activates G-protein –> G-protein activates a membrane bound enzyme –> the enzyme catalyses the production of the second messenger –> second messenger activates a kinase –> which activates another kinase –> eventually leading to a cellular response.

Question 10

When does a muscle contract?

Answer 10

When actin fibres are pulled and slide past myosin fibres. This process requires Ca2+ and ATP.

Question 11

What is myosin?

Answer 11

A molecular motor that converts chemical energy (ATP) to mechanical energy (movement) in order to pull on the actin fibres.

Question 12

What is the process of contraction of uterine endometrium?

Answer 12

1) Intracellular Ca2+ increases –> 2) Ca2+ binds to and activates calmodulin, forming calcium calmodulin (CaCM) –> 3) CaCM then binds to and activates the myosin light chain kinase (MLCK) –> 4) transfer of phosphate to myson heads, activating myosin head ATPases

Question 13

Where does the calcium come from?

Answer 13

Stored in the ER and mitochondria within the cell. Protein pumps move calcium out of the cytoplasm into the ER, mitochondria or extracellular fluid.

Question 14

What are heterotrimeric G proteins?

Answer 14

So called because they are made up of three different proteins: alpha, beta and gamma.
The heterotrimeric G protein is the inactive form of the G protein. When we activate it, the heterotrimeric G protein splits into alpha and By.

Question 15

What is the role of the a and By subgroups?

Answer 15

a subunit –> interacts with plasma membrane enzymes
By subunit –> perform signalling roles: ion channels, activate other kinases, activate regulatory mechanisms in the cell

Question 16

What are the three main types of a subunits?

Answer 16

• G-alpha-s –> stimulates production of cAMP
• G-alpha-i –> inhibits production of cAMP
• G-alpha-q –> increase diacylglycerol (DAG) and inositol triphosphate (IP3) production

Question 17

How do b2 agonists cause relaxation of the myometrium?

Answer 17

b2 acts upon the b2 receptor, causing a conformational change that then activates a G-alpha-s subunit –> the a subunit binds to and activates a membrane enzyme called adenylate cyclase –> adenylate cyclase catalyses the conversion of ATP to cyclic AMP –> cAMP activates phosphokinase –> PKA catalyses the phosphorylation of MLCK, inactivating it

Question 18

How does NO cause relaxation of the myometrium?

Answer 18

NO binds to soluble guanylyl cyclase (GC) inducing a conformational change and activating the enzyme –> this enzyme catalyses the conversion of guanisine triphosphate (GTP) to cGMP –> cGMP activates a kinase enzyme called phosphokinase G (PKG) –> PKG phosphorylates MLCK and turns it off –> PKG also phosphorylates myosin light chain phosphatase, activating it and catalysing the removal of phosphate from the myosin light chain

Question 19

What is desensitisation?

Answer 19

This is the rapid signal attenuation in response to stimulation of cells by receptor agonists.

Question 20

Why does desensitisation occur?

Answer 20

Change in receptors (phosphorylation), down regulation of receptors (internalisation/reduced expression), depletion of mediators, increased metabolic breakdown

Question 21

How does phosphorylation produce desensitisation?

Answer 21

Specific membrane-bound GPCR kinases (GRKs) phosphorylate the receptors –> acts as a binding site for B-arrestin (an intracellular protein that blocks the interaction between the receptor and G-proteins –> desensitisation

Question 22

How does internalisation lead to desensitisation?

Answer 22

Arrestin binding also causes internalisation (endocytosis) of the GPCR in a vesicle through two pathways:
1) Resensitisation: dephosphorylation (by protein phosphatases) and reinsertion into the plasma membrane
2) Degradation/inactivation: trafficking to the lysosomes for destruction

Question 23

What are some second messengers produced by GPCR activation?

Answer 23

Cyclic AMP, diacylglycerol and inositol triphosphate.