Secretory and Endocytic Pathways

Question 1

What do proteins that are targeted to the ER have?

Answer 1

N-terminal signal sequences.

Question 2

What are signal sequences recognised by?

Answer 2

The signal recognition particle. A cytosolic ribonucleoprotein complex.

Question 3

What does the SRP do?

Answer 3

Pauses translation to prevent proteins with signal sequences from folding in the cytosol.

Question 4

What is Sec61?

Answer 4

Where the ribosome binds to displace SRP. Forms a pore in the ER membrane allowing translocation of the protein.

Question 5

What is BiP?

Answer 5

Binding immunoglobin protein (ER luminal HSP70 chaperone). Required for translocation to the ER. Assembly of non-glycosylated proteins.

Question 6

What is glycosylation?

Answer 6

OG chain is added by oligoaccharyltransferase to asparagine residues. Associated with Sec61 translocon.

Question 7

What is calnexin?

Answer 7

A chaperone which prevents proteins folding and aggregating together.

Question 8

What does trimming do?

Answer 8

Removes 2 glucose residues, leaving a single one. Allows the correct folding.

Question 9

What is ERAD?

Answer 9

Helps prevent the accumulation of misfolded proteins in the ER which could otherwise aggregate. Removal of mannose residues acts as a molecular clock, required for the addition of glucose.

Question 10

What is ATF6?

Answer 10

An ER associated membrane protein. ER stress induces cleavage, releasing the N-terminal into the cytosol.

Question 11

What foes AFT6(N) do?

Answer 11

A transcription factor that induces expression of proteins involved in ER folding.

Question 12

What is PERK?

Answer 12

An ER-resident transmembrane kinase. Stress causes PERK to phosphorylate eIF2a, inhibiting mRNA translation.

Question 13

What is IRE1?

Answer 13

A ER transmembrane protein with endoribonuclease activities. Cleaves XBP1 mRNA which promotes expression of genes regulating lipid biosynthetic enzymes.

Question 14

Name a combination treatment for cystic fibrosis

Answer 14

Lumcaftor + ivacaftor

Question 15

name two other genetic diseases associated with the ERAD pathway?

Answer 15

osteogenesis imperfecta and a1-antitrypsin deficiency.

Question 16

Which virus hijacks the ERAD pathway to escape immune recognition?

Answer 16

HCMV by preventing HMC 1 molecules from reaching the plasma membrane.

Question 17

What do rab proteins do?

Answer 17

bring together membranes that are to fuse

Question 18

Which toxins can hijack multiple components of the endocytic and secretory pathways to access the ER and use ERAD machinery to access the cytosol?

Answer 18

Cholera and Ricin

Question 19

What does sec12 do?

Answer 19

Catalyses the GDP-GTP exchange on Sar1 causing it to bind to the membrane. It can then recruit sec23-24 to the ER membrane and recuit cargo proteins. Sec 13-31 drive budding.

Question 20

What is ERGIC-53?

Answer 20

A receptor which binds to soluble glycoproteins to incorporate them into COPII vesicles.

Question 21

What is CLSD?

Answer 21

Cranio-lenticulo-structural dysplasia. Skeletal defects and facial abnormalities caused by mutations in sec23a.

Question 22

What do many ER resident luminal proteins have?

Answer 22

A KDEL retrieval motif.

Question 23

What happens to N-linked oligosaccharides in the Golgi?

Answer 23

Modification by removal of 3 mannoses.

Question 24

what causes I-cell disease?

Answer 24

Mutations in N-acetylglucosamine-1-phosphotransferase. Loss of mannose-6-phosphate modification and secretion of lysosomal hydrolyses

Question 25

What activates signalling cascades?

Answer 25

EGF binding by EGF receptors.

Question 26

What causes Familial Hypercholesterolaemia?

Answer 26

Disruption of the LDL receptor resulting in CVD.