M&R - Receptors in Cell Signalling

Question 0

What is a receptor?

Answer 0

A molecule that recognises a specific ligand or family of ligands
The ligand binding brings about regulation of a cellular process.

Question 1

What is a ligand?

Answer 1

A small molecule that binds to a receptor site that’s may produce activation of a receptor or may bind to the receptor site without causing activation

Question 2

What is an acceptor?

Answer 2

Molecules that their basic function can be carried out without the interaction of a ligand (NOT receptors)

Question 3

Where must the receptor be if receiving a hydrophilic signal?

Answer 3

On the cell surface

Question 4

Where must the receptor be for a hydrophobic signal?

Answer 4

Intracellular receptor

Question 5

How are receptors classified?

Answer 5

According to the agonist and then sub classified on the basis of affinity

Question 6

What are 5 similarities between receptor binding sites and enzyme substrate binding sites

Answer 6

1. Binding at both sites is specific
2. Specificity is governed by the shape of the site
3. Specificity of binding = specificity of regulation
4. Binding is most often reversible
5. Ligand binding and allosteric sites on enzymes induces a conformational change

Question 7

What are some differences between receptor binding and enzyme sites?

Answer 7

1. Affinity of ligand binding at receptor sites is higher than the binding at enzyme sites
2. The ligand bound to a receptor site is not modified chemically wheras the substrate bound in an enzyme AS is modified

Question 8

What are the 4 common mechanisms for receptor action?

Answer 8

1. Membrane bound receptors with integral ion channels
2. Membrane bound receptors with integral enzyme activity
3. Membrane bound receptors which couple effectors through transducing proteins
4. Intracellular receptors for hydrophobic ligands

Question 9

Briefly describe how membrane bound ion channels with integral ion channels work?

Answer 9

Ligand binding results in conformational change and opening of ion channel which permits ion flow down EC gradient.
E.g nicotinic acetyl choline receptors

Question 10

Briefly describe how membrane receptors with integral enzyme activity work

Answer 10

This is when the agonist binding causes a conformational change which activates an intrinsic enzyme activity
E.g tyrosine kinase linked receptors

Question 11

Explain how seven transmembrane domain receptors work

Answer 11

Receptor binding results in a conformational change which activates transducing molecule (G protein ) These couple to effector molecules ie enzyme to bring about change
E.g ATP –> cAMP

Question 12

Briefly describe how intracellular receptors work

Answer 12

Hydrophobic ligands penetrate PM and bind to cytoplasmic or nuclear receptors. Chaperone protein dissociates and receptors translocates to the nucleus where it binds to DNA control regions - regulating gene transmission

Question 13

What is amplification?

Answer 13

By the stimulation of an enzyme this causes modification of thousands of substrate molecules - enzyme cascade!

Question 14

What is phagocytosis?

Answer 14

Permits the clearance of damaged cellular material
Particle binds to PM receptors
Cell extends pseudopods which internalise the particle
Phagosome fuse with lysosomes to form phagolysosomes in which the material is degraded

Question 15

What is pinocytosis?

Answer 15

Invagination of the PM to form a lipid vesicle

Permits the uptake of impermeable Extracellular solutes

Question 16

What is receptor mediated endocytosis?

Answer 16

Subtype of pinocytosis

Specific binding or molecules to cell surface receptors permits selective uptake into the cell

Question 17

Where are receptors located on the plasma membrane?

Answer 17

Over the coated pits

Question 18

Describe the process of cholesterol uptake

Answer 18

LDLs - apoprotein B on the surface - recognised by LDL receptors (clustered over coated pit) these invaginate and pinch off from PM to form coated vesicles. They are quickly uncoated and fuse with ENDOSOMES (pH of these are low due to ATP - H+ pump) at this low pH ligand and receptor uncouple

Question 19

What happens to the LDL receptor after uncoupling in the endosome?

Answer 19

It buds off as a vesicle to be recycled

Question 20

What happens to the free LDL after the endosome?

Answer 20

Fuses with lysosomes and the cholesterol esters are hydrolysed into Cholesterol and fatty acids

Question 21

What is the structure of the coated pit?

Answer 21

Triskellion (clathrin and 2 light chains)
Forms a basket like structure of hexagons and pentagons
Assembly is spontaneous

Question 22

What might some mutations that affect LDL uptake be?

Answer 22

Receptor deficiency
Non functional receptor
LDL receptors located away from the coated pit so no internalisation of the LDLS

Question 23

How is iron uptaken into the cell?

Answer 23

2Fe3+ ions bind to apotransferrin forming transferrin
This binds to receptors and is internalised
On reaching the endosome the Fe2+ ions are released from transferrin but apotransferrin remains associated with the receptor until it is sorted and recycled back to PM and is dissociated at surface

Question 24

How is insulin uptaken?

Answer 24

Insulin receptors congregate over CP when insulin is bound.

In the endosome the insulin remains bound to the receptor and the complex is targeted to the lysosome for degradation

Question 25

What is transcytosis?

Answer 25

Some ligands that remain bound to receptors are transported across the cell e.g maternal immunoglobulin transported to bile In the liver during transport the receptor is cleaved

Question 26

How do viruses take advantage of the coated pit?

Answer 26

They exploit the endocytosis pathway by binding to receptors in the PM. Once in the endosome the viral membrane is able to fuse with the endosomal membrane releasing viral RNA into the cell