Protein Trafficking Flashcards Preview

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Flashcards in Protein Trafficking Deck (62)
1

Which of the following pathways does not utilize vesicular transport
a) Golgi --> ER
b) secretory vesicles --> cell exterior
c) lysosome to late endosome
d) nucleus to cytosol

d) gated transport

2

What are the two ways that a signal can be built into a protein?

1) signal sequence (continuous linear sequence)
2) signal patch (3D conformation of signal sequence)

3

What three types of nucleoporins are found in NPC?

TM ring proteins (anchor NPC to envelope)
scaffold nucleoporins (form layered ring structures)
channel nucleoporins (line central pore)

4

How do the receptor-like fibrils that protrude from NPC differ?

On nuclear side, converge to form basket like structure

5

What size of molecules diffuse into nucleus freely via aqueous pores?

5kDa or less

6

What size proteins cannot enter nucleus via passive diffuse

50kDa and above

7

Describe the role of Ran in nuclear import

In nucleus, Ran-GTP binds to import receptor and cargo is released.
Once import receptor back in nucleus, Ran-GAP dephosphorylates Ran-GTP and it dissociates.
Import receptor can pick up cargo again.

8

Describe the role of Ran in nuclear export

Ran-GTP promotes cargo binding to export receptor

9

What is NFAT?

nuclear factor of activated T-cells

10

Describe the cycle of NFAT during T cell activation

- T cell activation causes high calcium in active T cell.
- Calcineurin binds and dephosphorylates NFAT, exposing its nuclear import signal.
- NFAT imported, activates IL-2 gene transcription.
- Ca++ eventually decreases
- Calcineurin drops off and NFAT is phosphorylated (using ATP) exposing nuclear export signal

11

What is the role of IL-2?

Stimulates clonal expansion of memory T cells

12

How does cyclosporine work to prevent organ rejection?

Inhibits calcineurin, prevents phosphorylation of NFAT and therefore NFAT translocation into T cells

13

What occurs to collagen polypeptide after translation? (up until ER)

Signal sequence on polypeptide is targeted to ER by signal recognition particle

14

Describe co-translational translocation

- Signal recognition particle binds to signal sequence, and translation is paused until attaches to SRP receptor in ER membrane
- Translation continues and translocation begins

15

What does the N-terminal signal sequence also act as?

START-TRANSFER sequence

16

The start-transfer sequence binds to ___________ and then is discharged into the bilayer once translocation is complete

active translocator

17

Describe the mechanism by which LDL receptor is placed in plasma membrane (4 steps)

- Start transfer sequence opens translocator
- Stop transfer sequence enters translocator
- Translocator opens and discharges start transfer sequence laterally

(one pass transmembrane protein)

18

What three changes occur in ER lumen that lead to formation of the triple helix in collagen?

1) signal peptide of N terminus dissolves
2) hydroxylation of lysines and prolines
3) glycosylation (addn of glucose/galactose monomers onto hydroxyl groups) on lysines

19

Why does lack of Vitamin C cause scurvy?

Because Vitamin C is a cofactor in the hydroxylations of lysines and prolines during the formation of the triple helix of collagen therefore collagen triple helices are loose

20

Does stop transfer sequence stop translation?

NO

21

When a single pass transmembrane protein is inserted into the ER membrane, what determine that the N terminus is on the cytosolic side?

If more positively charged AA immediately proceed hydrophobic core of start transfer sequence

22

How does a multipass transmembrane protein get inserted

same process as any transmembrane protein but translocator does not discharge start transfer sequence laterally until FINAL stop transfer sequence has entered

23

What is the significance of coated vesicles? Name three types

Different protein coats select different cargo. COPI, COPII, clathrin

24

After being processed in the golgi apparatus, what happens to procollagen?

It is packaged by COP1 proteins into a secretory vesicle destined for extracellular space

25

What occurs in the regulated secretory pathway?

Selected proteins in TGN are directed into secretory vesicles where proteins are concentrated and stored until extracellular signal stimulates their secretion

26

The human pancreas has the largest capacity for protein synthesis of any organ in human body. What is much of capacity used for?

synthesizing digestive enzymes in acinar cells

27

Which of the following enzymes is not stored in pancreas?
a) alpha amylase
b) beta lactamase
c) lipase
d) RNAse
e) DNAse

b

28

What is a pancreas consensus element?

They are enhancer regions found on genes for digestive enzymes that regulate transcription of mRNAs

29

________, a transcription factor, binds to pancreas consensus elements and essential for __________________

PTF-1, expression of digestive enzymes

30

What is the endocrine function of the pancreas?

Produce and secrete insulin and glucagon

31

What occurs in exocrine pancreatic insufficiency?

Pancreas is damaged and cannot produce enough enzymes to digest food --> fail to get nutrition from food eaten

32

Which of the following is NOT a disease caused by exocrine pancreatic insufficiency?
a) chronic pancreatitis
b) celiac disease
c) crohn's disease
d) diabetes
e) all of the above are caused by EPI

e)

33

in Zollinger Ellison, what causes EPI?

acid mediated deactivation of pancreatic enzymes

34

What causes EPI in Celiac disease?

Decreased pancreatic stimulation

35

Obstruction of the main pancreatic duct can result in?

Tumor

36

What type of transport do clathrin coats mediate?

receptor-mediated vesicular transport

37

What do clathrin coated vesicles accomplish in TGN?

1) sort lysosomal proteins for transport to lysosomes
2) sort substrances for storage in secretory vesicles

38

What do clathirin coated vesicles accomplish at plasma membrane?

Used for uptake of extracellular material via RECEPTOR MEDIATED ENDOCYTOSIS

39

Digestive enzyme exocytosis is stimulated by what?

neurohormal agents such as acetylcholine

40

Clathrin coats mediate formation of secretory vesicles also called what?

zymogen granules

41

When someone eats, the exocrine pancreas must replenish stores of digestive enzymes. This triggers three processes:

1) unfolded protein response - inc synth of chaperones and foldases
2) upregulation of systems involved in degradation of un/mis folded proteins
3) ER-associated protein degradation = required to rid cell of mis/un folded toxic proteins

42

The adaptive unfolded protein response has 3 functions

1) inc expression and funcn of chaperones and foldases
2) activate ERAD
3) global reduction in translation of mRNA everywhere ELSE

43

Where does calnexin, the membrane bound chaperone bind to incompletely folded proteins?

1 terminal glucose on N-linked oligosaccharide

44

Where are proteins glycosylated ? (location of cell)

ER lumen

45

What happens to protein once it is bound by calnexin?

It is trapped in the ER to refold, terminal glucose is removed in process. After released, glucose transferase determines if folded properly. if not, glucose added to restart process

46

How are proteins degraded through ERAD?

Proteasome

47

Liver is central to the regulation of what?

Cholesterol levels - synthesizes for export and removes from body by converting to bile salts

48

Describe LDL cholesterol

"bad", main carrier of cholesterol in circulation, main source of build up and blockage in arteries

49

Describe HDL cholesterol

good, helps remove cholesterol from arteries

50

Describe triglycerides

Another form of fat in blood that can raise your risk of heart disease

51

What molecule is recognized by LDL receptor for removal of LDL from circulation and delivery of cholesterol to cell?

apolipoprotein B10

52

Cholesterol is a precursor for (3)

steroid hormones, bile acids, vitamin D

53

Receptor mediated endocytosis of LDL

LDL binds to LDL receptor in ER membrane and is endocytosed through clathrin coated pit

54

What type of mutation can lead to hyperchoelesteremia?

LDL receptor protein with defective coated pit binding site

55

Familial hypercholesteremia is a ___________ disorder caused by mutations in LDL receptors

autosomal dominant

56

Heterozygotes for FH are present in 1 / ______ people whereas homozygotes are 1 / _____ people

500, million

57

In homozygotes for FH, sudden death and acute MI may happen as early as ______ years old

1-2 years

58

In heterozygotes for FH, CAD in men develops in _____

40s - women delayed by 10-15 yrs

59

How is free cholesterol released in bloodstream (start in ER)

LDL endocytosed --> vesicle uncoated -> fusion with endosome --> lysosome --> free cholesterol released

60

Lysosomes contain what type of pump

ATP driven H+

61

What tag diverts proteins to lysosome

mannose 6 phosphate

62

What are the three paths towards lysosomal degradation

endocytosis
autophagy
phagocytosis