Receptor structure and cell signalling

Question 1

Define Autocrine Signalling

Answer 1

cell secrets hormone/chemical messenger which binds to receptor within the same cell

Question 2

Define Paracrine Signalling

Answer 2

cell secrets hormone/chemical messenger which binds to receptor in neighbouring cell

Question 3

Define Endocrine Signalling

Answer 3

cell secretes hormone/chemical messenger which travels through circulatory system before it binds to receptor of distant cell

Question 4

4 things to consider when thinking of cell signalling

Answer 4

1. Specificity
2. Regulation
3. Amplification
4. Stop Mechanism/Desensitisation

Question 5

Define Specificity

Answer 5

Signal molecule fits in active site of complementary receptor, this is stabilised with weak non covalent bonds and tissue specific expression such as dimerisation provides an even more specific response

Question 6

Define Amplification

Answer 6

When enzymes activate enzymes producing secondary molecules and further enzyme cascades, increasing the signal strength by several orders of magnitude in milliseconds

Question 7

Define Desensitisation

Answer 7

Receptor activation triggers feedback loop that terminates the signal, this can be through cleaving off or altering the receptor, by blocking the receptor with an antagonist, breaking down the signal molecule or diverting it away from receptor.

Question 8

Define Integration

Answer 8

when two signals have the opposite effect on a metabolic characteristic such as a secondary messenger this results in an integrated regulatory response where fine tuning can alter the concentration of signalling molecule. think of glycolosis and gluconeogenesis for control of blood glucose concentration

Question 9

Define Integration

Answer 9

when two signals have the opposite effect on a metabolic characteristic such as a secondary messenger this results in an integrated regulatory response where fine tuning can alter the concentration of signalling molecule. think of glycolosis and gluconeogenesis for control of blood glucose concentration

Question 10

Define Compartmentation

Answer 10

compartmentalisation of the cell enables efficient and specific signalling response, certain areas of the cell will have certain receptors enabling the signaling molecules to be directed efficiently

Question 11

What is the general structure of a G-Protein Coupled Receptor?

Answer 11

Single amino acid chain that loops the membrane 7 times. Amino terminus is external while carboxy terminus is cytoplasmic.

Question 12

What are the key domains on a GPCR that interact with G-proteins?

Answer 12

Cytoplasmic loop 3 (C3 domain) and carboxy terminus.

Question 13

List the 5 major classes of GPCRs

Answer 13

1. Rhodopsin/beta2 adrenergic receptor,
2. Glucagon/ Secretin receptor
3. Glutamate/ Metabotropic neurotransmitter receptors
4. Adhesion
5. Frizzled/Taste 2 (wnt)

Question 14

How are GPCR tethered to the cell?

Answer 14

by lipid side chains/Protein lipidation

Question 15

what are the 3 major structural components of G alpha sub-unit?

Answer 15

GTPase domain, helical domain and 3 Switch region

Question 16

List the 4 methods of termination of the cellular receptor

Answer 16

1. Ligand dissociation,
2. Hydrolysis of G alpha GTP
3. Down regulation by endocytosis
4. Phosphorylation of receptors (2 types)

Question 17

How does Ligand dissociation cause termination of cellular recepor

Answer 17

conversion of GaGDP to GaGTP causes dissociation constant (Kd) of hormone-receptor complex to increase shifting equilibrium towards dissociation

Question 18

How does Hydrolysis of GaGTP cause termination of cellular receptor

Answer 18

hydrolysis of GTP toGDP causes G alpha to dissociate from effector molecule therefore terminating the signal

Question 19

How does endocytosis work to cause cellular response to be down regulated

Answer 19

Endocytosis of signal molecules reduces the concentration of signal molecules in the cell therefore reducing receptor binding this is especially common near the plasma membrane

Question 20

How does Phosphorylation terminate the cellular receptors?

Answer 20

Phosphorylation of GCPR terminates the signal as it blocks the active site from signal molecules binding. this can be either homologous or heterologous desensitisation depending on kinase utilised

Question 21

what is homologous desensitisation

Answer 21

Homologous desensitisation is when kinase phosphorylating the receptor is specific to that receptor, therefore only terminating that receptor

Question 22

what is heterologous desensitisation

Answer 22

when generalised kinase phosphorylates receptor therefore all GCPR are effected

Question 23

what are the 3 general states of the GCPR mechanism, and explain what is happening in each.

Answer 23

Inactive state( trimeric protein isolated)
Receptor activated state( trimeric protein bound to receptor after conformational change)
Effector activated state ( G alpha subunit dissociated from G betagama and bound to GTP => effector binding)

Question 24

describe the first stage of GCPR mechanism when ligand has just bound

Answer 24

Ligand binding causes conformational change in receptor this enables Galpha subunit to bind. G alpha subunit then goes through conformational change causing GDP to dissociate

Question 25

describe the second stage of GCPR mechanism when effector is activated

Answer 25

GTP binds to Galph causing further conformational change and dissociation from G beta-gamma subunit, binding to the effector protein to activate it

Question 26

describe the third stage of GCPR mechanism when trimeric G protein returns to its inactive state

Answer 26

Hydrolysis of GTP=>GDP causes G alpha to dissociate from effector protein and reassociate with the G beta gamma subunit returning to its inactive state ready to react to incoming ligand on receptor