Endocytosis & Protein Degredation Flashcards Preview

Molecules to Medicine III > Endocytosis & Protein Degredation > Flashcards

Flashcards in Endocytosis & Protein Degredation Deck (33)
1

What are the 2 major routes of small volume endocytosis? How do they work?

Phagocytosis
- Multicellular organisms
- Usually by specialized cell (i.e. macrophage/ neutrophil)
- Cells recognize foreign organisms -> engulf-> deliver to lysosomes for degradation
- Recognize apoptotic cells

Pinocytosis
- Associated with vesicle uptake of (by) specific ligands and receptors

2

What are the types of vesicles used in pinocytosis?

Clathrin coated &
Caveolae

3

How are clathrin coated vesicles formed?

Cargo molecules (LDL) bind transmembrane receptor (LDLR) -> transmembrane receptor recognizes and binds adaptor protein (w/ motif in cytoplasm) -> Adaptor complex of proteins forms -> Enables clathrin coat to assemble on vesicle budding from plasma membrane (or golgi to secretory pathway)

Vesicle is pinched off from membrane by dynamin
- adaptor complex and clathrin rapidly dissociate

4

What is the function of dynamin

Pinch clathrin coated vesicles off from golgi or plasma membrane

5

What is the progression of phagocytosis of LDL?

LDL-receptor binding -> coated vesicle (clathrin and adaptor complex dissociation) -> early endosome -> late endosome (LDLR returns to membrane) -> lysosome

6

What types of molecules enter through caveolae?

cholera, tetnus, folic acid,

7

How many caveolins are in each vessicle?

144

8

Where is caveolin 3 expressed? and what diseases can its mutation cause?

in skeletal and cardiac muscle
- limb girdle disese
- Rippling Muscle disease

9

What can macrophages degrade?

EVERYTHING (except cholesterol)
mis-folded protiens
damaged organelles
good and bad endocytosed materials

10

Why must improperly folded proteins be degraded?

They may aggregate and wreak HAVOC!

11

What are the 3 major pathways of protein degradation?

Ubiquitin-proteasome system (UPS)
lysosome
autophagy

12

What is autophagy used for?

- degradation of long lived proteins & entire organelles
- important in development
- Req for adaptation to environmental stresses (i.e. starvation)

13

Describe the ubiquitin-proteasom system (UPS)

- Proteins deglycosylated after retrotranslocation out of ER
- Ligase enzymes E1, E2, and E3 bind & activate ubiquitin
- Polyubiquinated=> targeted to proteasome for degradation

14

Describe the action of a proteasome

huge complex of proteis -> unwinds misfolded proteins, feed into compartment -> where cut into 7--9 amino acid lengths

15

What % of cellular protein is proteasome?

~1%

16

How many E1, E2, & E3 genes do humans have? What is the function of each?

E1: 1 - activate ubiquitin
E2: ~50 - Receive U from E1, transfer to E3
E3: ~500 - attaches U to lysine in protein - substrate specificity

17

How many ubiquitins are required for degradation?

at least 4 in a chain (polyubiquitination)

18

What are the other functions of ubiquitin?

multiubiquitination: mutiple single ubiquitins at several locations on a protein
aka: mono/multi ubiquitins- regulatory signals (u of histones, TFs to reg transcription

19

What is the function of chaperone proteins?

Help with proper folding of newly synthesized proteins

20

What are 2 examples of chaperone proteins?

hsp60
hsp70
(heat shock protein)

21

How does hsp70 function?

prevents aggregation by binding to exposed hydrophobic areas in incompletely folded amino acids

22

How does hsp60 function?

acts as an isolation chamber (prevent aggregation and refold) in barrel-shaped structure

23

What is the generic name for proteins that bind sugas? Give 2 examples

lectins: calnexin & calreticulum

24

What percentage of proteins are folded in the rER? Where are these proteins destined?

~30%
transmembrane proteins, vesicular transport and secretion

25

Describe the protein folding pathway involving calnexin, calreticulum and a glucosyltransferase.

calnexin and calreticulum bind oligosaccharide chain if a glucose is present-> When glucose reomved by glucosidase (GT) C & C release protein -> if correctly folded allowed to exit ER

-> if incorrectly folded-> glucose added back on by glucosyltransferase and cycle repeats

- at a certian point (unclear when/why) protein is identified as unsaveable, "times out" and is translocated from ER, destined for degredation

26

Describe a proteasome

~2million dalton protein
- central cylinder with cap a each end (recognize polyubiqutiinaiton) -> use ATP to unfold protein- feed into cylinder

Degrades only proteins!

27

How many amino acids does ubiquitin have?

76 - HIGHLY CONSERVED!!
~1% of cellular protein

28

Describe the function of a lysosome

- degrade extracellular materials& some intracellular components

29

What ca lysosomes degrade

everything: proteins, lipids and sugars

30

What is the path to a lysosome?

monoubiquinated plasma proteinstansferec by late endosome/ multivesicular body to lysosome
- multovesicular body (prelysosomal compartment with molecules slated for destruction in lumen)

lysosomal membrane proteins and transporters protected from degradation (error here = lysosomal storage disorder)

31

What is autophagy?

when components of cell are broken down and reused
- normal turnover, damaged organelles, starvation
- uses double membrane around organelle- fuses with lysosome-> contents degraded

32

What is ERp57

protein folding enzyme
thiol oxoreductase - allows formation of disulfide bonds

33

What is UDP?

Folding sensor involved in quality control
glucose:glycoprotein glucosyltransferase