Receptors and Diseases

Question 1

Why are receptors required?

Answer 1

To respond to environment
spatial patterning
apoptosis
differentiation
proliferation

Question 2

How can receptors be classified?

Answer 2

Cell specific: synaptic or contact dependant

Cell type specific: Endocrine or paracrine

Question 3

What are the main types of receptors?

Answer 3

GPCR
Enzyme coupled
Adhesion
Pathogen recognition

Question 4

How many types of GPCR are there?

Answer 4

800

Question 5

What is Jansens metaphyseal chrondrodysplasia?

Answer 5

Overactivation of kidney PTHr GPCR
Raises cAMP
Lack of Ca/P regulation
dwarfism

Question 6

What is Hashimoto’s disease?

Answer 6

Antagonistic antibodies on TSHR
Decrease cAMP
Hypothyroidism
Weight gain

Question 7

What is Grave’s disease?

Answer 7

TSHR agonist antibodies
Hyperthyroidism
Weight loss

Question 8

Which toxins target GPCRs?

Answer 8

Cholera overactivates Gαs by ADP-ribosylation
Pertussis inhibits Gαi by ADP-ribosylation
Both raise cAMP

Question 9

What is McCune-Albright Syndrome?

Answer 9

Somatic non-receptor defects in GPCRs

Cafe-au-lait phenotype produced by variation in melonocyte stimulating hormone

Question 10

How is Pseudohypoparathyroidism caused?

Answer 10

Monoalleic inheritance and epigenetic silencing of PHPI gene causing loss of PTHr Gαs function

Question 11

What are the different types of adhesion receptors?

Answer 11

Ig superfamily
cadherins
integrins
selectins
proteoglycans

Question 12

What types of interactions do adhesion receptors mediate?

Answer 12

Homo/heterotypic

Cell-cell and cell-ECM

Question 13

What type of adhesion receptor interactions are highest affinity?

Answer 13

homotypic

Question 14

What interactions do integrins have?

Answer 14

αβ dimers bind RGD motifs in high affinity clusters

Question 15

What type of interactions do selections mediate?

Answer 15

transient, low affinity binding of sialyl lewis sugars

Question 16

Which organisms use adhesion receptors?

Answer 16

multicellular organisms for spatial patterning in embryonic development

Question 17

What organisms have microbial receptors?

Answer 17

metazoans

Question 18

What are the microbial receptors?

Answer 18

Surface Pattern Recognition receptors are toll like and carbohydrate binding lectins

Question 19

What do microbial receptors do?

Answer 19

Bind PAMPS to stimulate cytokines and immune response

Question 20

What affect do microbial SNPs have?

Answer 20

Increases susceptibility to microorganisms such as canidida

Question 21

How are microbial receptors hijacked by pathogens?

Answer 21

HIV uses CD4 to enter cell

Listeria uses integrins for phagocytosis to release toxin into cell

Question 22

What cellular responses do RTKs have?

Answer 22

Phosphorylation cascades to control ion balance, metabolism, glucose uptake, gene expression

Question 23

What signalling molecules do RTKs respond to?

Answer 23

Growth signals

Insulin

Question 24

How can type 2 diabetes be caused?

Answer 24

Desensitisation of receptor by FFA/excess glucose,
tyrosine phosphatases,
Clathrin dependant endocytosis
Downregulation of IRS by S/T phosphorylation
PI3K antagonist hormones produced by adipose tissue
IRS polymorphisms

Question 25

How is type 1 diabetes caused?

Answer 25

Autoimmune attack of pancreatic β cells producing insulin

Question 26

What are the main targets of insulin RTKs?

Answer 26

IRS1 for mitogenic activity | IRS2 for Glut4 translocation

Question 27

What cellular responses does insulin cause?

Answer 27

Protein and glycogen synthesis Transcription Exposure of Glut4 receptos

Question 28

What is the structure of the Insulin receptor?

Answer 28

Permanent extracellular dimer of αβ-βα subunits connected by disulphide bonds

Question 29

How common are RTK receptors?

Answer 29

1/3 of all cell receptors

Question 30

How are RTKs activated?

Answer 30

Ligand binds causing conformational change Internal homodimerisation and transautophosphorylation Recruits small G proteins in MAPK Ser/Thr kinase cascade

Question 31

How can RTK mutations cause cancer?

Answer 31

Point mutations or deletion produces ligand independance, lack of autoinhibition

Question 32

What perecntage of cancers are caused by viruses?

Answer 32

25%

Question 33

How common are Ras mutations?

Answer 33

90% of tumours have no GTPase | 30% caused by single substitution

Question 34

What cellular responses are induced by RTK-MAPK activation?

Answer 34

Transcription factors, cytoskeleton Protein kinases

Question 35

How can RTK cancers be treated?

Answer 35

Inhibitors of MAPK cascade | Inhibition on receptor by antagonistic antibodies