Secretory Pathway 1: ER

Question 1

Name ER functions

Answer 1

• Membrane and secretory protein synthesis
• Post-translational modifications
• Chaperone-mediated protein folding
• ER associated degradation and stress
• Autophagy

Question 2

Whats in the EM system? name organelles

Answer 2

endosome, nuclear membrane (extension of ER), lysosome, golgi, ER, plasma membrane NOT mito or peroxysome

Question 3

how does stuff get into the nucleus?

Answer 3

nuclear pore, bw inner and outer, usually its ER lumen between there

Question 4

JUST rer main functions

Answer 4

secreted and membrane (on cyto side) proteins

Question 5

SER and rer functions

Answer 5

1. synth of phospholipids/cholesterol
2. ca2+ storage (mainly SER)
3. antigen presentation

Question 6

just SER functions

Answer 6

1. steroid synth
2. bilirubin conjugation
3. detox
4. cop2 vesicle formation

Question 7

3 types of client proteins and examples (always secreted or in ER)

Answer 7

client=made in ER
secreted out=peptide hormones, Igg, extracellular
integral membrane=receptors or cell adhesion
lumenal of EM system=ER chaperones, lysosomal hydrolases

Question 8

3 types of non client (made on free ribosomes…usually cytosolic or in other organelles)

Answer 8

cytosolic-contractile or soluble
peripheral membrane on cytoplasmic face-spectrin
nuclear, mitochrondrial

Question 9

where does post translational mod happen vs protein synth

Answer 9

protein synth on cyto side, post trans mod lumen side

Question 10

List the modifications that take place in ER post or during translocation

Answer 10

Glycosylation
Proline hydroxylation
S-S bond formation
Protein Folding
Subunit assembly
Quality control
Degradation

Question 11

How does ER translocate protein into lumen? how can it stay in membrane?

Answer 11

SRP bind to signal sequ on protein and direct/open transmembrane channels to thread into lumen of ER…if stop transfer sequence becomes ER membrane protein

Question 12

What is N-linked Glycosolation? When does it occur?
What are 2 examples?
what chaperones does it prep for?

Answer 12

1. oligosacharride (from ER) added to Asp-residue of protein (n linked) via olligosacuryl transferase
2. co translationally before folding
3. glycoproteins=insulin receptor and HIVgp160
4. calnexin and calreticulun

Question 13

chaperones promote what 2 things? how do they do the second?

lumen vs. cyotosol which is reducing and oxidizing?

Answer 13

folding and oxidation (stablizes).

oxidation: cytosol is reducing in comparison to oxidizing lumen which leads to S-S bond formation/covalent stabilization

Question 14

how many disulfides formed in proinsulin?

Answer 14

3

Question 15

What are the two types of chaperones in the RER? mechanisms?

Answer 15

1. Bip atp-ase. pushes hydrophobic inside protein by falling on and off h-phobic aa’s..(proinsulin is an example)
2. calnexin and calreticulun bind to glucose which eventually gets removed (HIVpg160 and other glycoproteins and insulin receptor)

Question 16

what are 2 examples of subunit formation in ER lumen

Answer 16

1. proinsulin hexamer

2. Igg heavy light chains

Question 17

ERAD…how does it occur?

in what disease is a mutant protein degraded entirely by ERAD? whats the mutant protein?

Answer 17

misfolded proteins will stay attached to chaperones (QC)>threaded out of ERM>UBQ ligase add UBQ>proteosome

CF, delta 508 CFTR cant regulate CL

Question 18

what protein in parkinson’s can be misfolded and how can you remediate?

Answer 18

synuclien. chaperones can buffer.

Question 19

what is ER stress? how can it be modulated and by which 3 factors

Answer 19

demand>capacity…can expand capacity like huge ER in insulin…
ATG6 IRE1 PERK regulate by turning on/off translation of necessary ER proteins

Question 20

What can deleting perk do to your insulin secreting cells?

Answer 20

cause buildup, not enough ERAD or folding proteins

Question 21

what protein creates S-S in lumen

Answer 21

protein disulfide isomerase