Endocytosis & Protein Degredation Flashcards Preview

Molecules to Medicine III > Endocytosis & Protein Degredation > Flashcards

Flashcards in Endocytosis & Protein Degredation Deck (33)
Loading flashcards...
1
Q

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

A

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
Q

What are the types of vesicles used in pinocytosis?

A

Clathrin coated &

Caveolae

3
Q

How are clathrin coated vesicles formed?

A

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
Q

What is the function of dynamin

A

Pinch clathrin coated vesicles off from golgi or plasma membrane

5
Q

What is the progression of phagocytosis of LDL?

A

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

6
Q

What types of molecules enter through caveolae?

A

cholera, tetnus, folic acid,

7
Q

How many caveolins are in each vessicle?

A

144

8
Q

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

A

in skeletal and cardiac muscle

  • limb girdle disese
  • Rippling Muscle disease
9
Q

What can macrophages degrade?

A

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

10
Q

Why must improperly folded proteins be degraded?

A

They may aggregate and wreak HAVOC!

11
Q

What are the 3 major pathways of protein degradation?

A

Ubiquitin-proteasome system (UPS)
lysosome
autophagy

12
Q

What is autophagy used for?

A
  • degradation of long lived proteins & entire organelles
  • important in development
  • Req for adaptation to environmental stresses (i.e. starvation)
13
Q

Describe the ubiquitin-proteasom system (UPS)

A
  • Proteins deglycosylated after retrotranslocation out of ER
  • Ligase enzymes E1, E2, and E3 bind & activate ubiquitin
  • Polyubiquinated=> targeted to proteasome for degradation
14
Q

Describe the action of a proteasome

A

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

15
Q

What % of cellular protein is proteasome?

A

~1%

16
Q

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

A

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

17
Q

How many ubiquitins are required for degradation?

A

at least 4 in a chain (polyubiquitination)

18
Q

What are the other functions of ubiquitin?

A

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

19
Q

What is the function of chaperone proteins?

A

Help with proper folding of newly synthesized proteins

20
Q

What are 2 examples of chaperone proteins?

A

hsp60
hsp70
(heat shock protein)

21
Q

How does hsp70 function?

A

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

22
Q

How does hsp60 function?

A

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

23
Q

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

A

lectins: calnexin & calreticulum

24
Q

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

A

~30%

transmembrane proteins, vesicular transport and secretion

25
Q

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

A

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
Q

Describe a proteasome

A

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

Degrades only proteins!

27
Q

How many amino acids does ubiquitin have?

A

76 - HIGHLY CONSERVED!!

~1% of cellular protein

28
Q

Describe the function of a lysosome

A
  • degrade extracellular materials& some intracellular components
29
Q

What ca lysosomes degrade

A

everything: proteins, lipids and sugars

30
Q

What is the path to a lysosome?

A

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
Q

What is autophagy?

A

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
Q

What is ERp57

A

protein folding enzyme

thiol oxoreductase - allows formation of disulfide bonds

33
Q

What is UDP?

A

Folding sensor involved in quality control

glucose:glycoprotein glucosyltransferase