Bio Lecture 8 Notes

Front 1

What happens in/on ER

Back 1

• proteins fold with help from chaperones

• Enzymes inside ER catalyze modifications

  
  

  • S-S bonds

  • N-glycosylation begins

  • Removal of SP (when it happens)

• some prots stay in ER, but most move to Golgi

Front 2

What types of Chaperone proteins are there

Back 2

HSP60 (forms barrel) and HSP70 (binds to hydrophobic regions), HSP70(aka BiP) is the major chaperone inside ER

Front 3

What is Ubiquitin addition

Back 3

• A marker protein found in cytosol that mark proteins that do not fold properly to be destroyed

• attaches to side chains of lysine

Front 4

What is Proteasome

Back 4

• large protein complex in cytosol that degrades ubiquitinylated proteins to fragments at expense of ATP

  
  
  • where much of intracellular proteins (misfolded, damaged, or proteins that have served their functions) are degraded

Front 5

What leaves a proteasome

Back 5

recycled ubiquitin and short peptide fragments

Front 6

What role do the recycled peptide fragments from proteasomes have

Back 6

fragments attach to T.M proteins and move through EMS to plasma membrane, allowing system to ID and target cells making unusual proteins

Front 7

Lysosomes vs. Proteasomes

Back 7

• lysosomes → material from outside

  
  

  • Only one molecule of ubiquitin targets proteins

  • Cytoplasmic proteins and organelles can be degraded in lysosomes under certain conditions

• Proteasomes → material from inside

Front 8

N-Glycosylation

Back 8

• When oligosaccacharides are added to side chains of Ser, Thr, or Asn

  
  
  • Only addition to Asn happens in ER

  • Begins in ER and ends in Golgi

    
    

    • In ER - oligo added to N of amide of Asn

    • In Golgi - oligo added to O in hydroxyl sides of Ser or Thr

Front 9

• What is the role of Golgi complex

Back 9

finish N-glycosylation, do O-glycosylation of glycoproteins, assemble sugars of proteoglycans (GAGs), and concentrate + sort proteins (@TGN)

Front 10

What are the three basic compartments in a stack

Back 10

• CGN (Cis) - include fusing vesicles

• medial sacs - between cis and trans

• TGN (trans) - include budding vesicles

Front 11

What is a marker enzyme

Back 11

enzymes unique to any one cell organelle or compartment - presence “marks” presence of that compartment/organelle

Front 12

How do proteins + lipids travel through Golgi

Back 12

• sac moves up, carrying cargo

• proteins from EMS travel from ER to golgi

  
  

  • Coated vesicles carrying protein bud off ER, travel to golgi and fuse with CGN

  • Exit out of TGN

Front 13

Which way do the vesicles in Golgi go?

Back 13

both anterograde and retrograde

Front 14

What do vesicles in Golgi carry

Back 14

• Cargo proteins (newly made proteins from ER)

• or Modification (marker) enzymes

Front 15

Where do proteins go after golgi

Back 15

• become part of EMS and/or leave cell

  
  

  • Some are transported in vesicles

  • Inside lumen or embedded in vesicle membrane

  • some leave cell or reach plasma membrane (secretory or default vesicles)

  • some go to other parts of EMS (lysosomes or other vesicles --> Golgi, ER, etc)

Front 16

what are Secretory vesicles

Back 16

• vesicles involved in regulated secretion found in area near plasma membrane

• only fuse with plasma membrane in response to signal (hormonal, concentration of Na, etc)

• signal usually causes increase in [Ca], triggers fusion, causing exocytosis

• Fusion results in: Contents outside cell and/or addition of material to cell membrane

Front 17

What are default vesicles

Back 17

• involved in constitutive secretion

• plasma membrane → fuse automatically and release contents

• no signal

Front 18

What model does the Golgi follow?

Back 18

hybrid of stationary and progression

Front 19

What do lysosomes contain

Back 19

• enzymes (acid hydrolases)

• substrates of the hydrolases (proteins to be degraded)

Front 20

How are proteins degraded in lysosomes

Back 20

• endo/phagocytosis

• autophagy

• Vesicle containing substrate fuses with vesicle containing hydrolytic enzymes

  
  

  • If substrate is T.M protein, the membrane containing it must end up entirely within the the lumen of the lysosome, as in autophagy

Front 21

What is Autophagy

Back 21

• when proteins/organelles come from cytoplasm, and are encircled by 2 bilayers of internal membranes

• Outer membrane fuses with a lysosome, leaving the material to be degraded entirely in the lumen of the lysosome

Front 22

How do hydrolases reach Golgi?

Back 22

• 1a. hydrolases made on RER; enter co-translationally

• 2a. hydrolases transported in vesicles to Golgi

Front 23

How are hydrolases identified and tagged for transport to lysosomes

Back 23

3a. since hydrolases for lysosomes have LS, enzymes add Mannose-6-P (in GOLGI)

Front 24

Role of M6P receptor

Back 24

• 4a. Receptor in special part of TGN binds proteins with M6P

• 5a. proteins with M6P and receptors accumulate in coated pits

• 6a. proteins bud off

• 7a. go to a sorting vesicle/endosome

• 8a. M6P receptors are recycled and go to Golgi

• 9a. Lysosomes with hydrolases add to old lysosome or form new ones

Front 25

I-cell disease

Back 25

• Lysosomal disease; enzyme that catalyzes formation of M6P

• defect in gene for enzyme that modifies ALL soluble hydrolysis (step 3a skipped)

  
  

  • Hydrolases never reach lysosomes (go to wrong part of golgi)

• Consequences: inclusion bodies form (vesicles full of undigested materials)

Front 26

Standard Lysosomal storage disease

Back 26

• when ONE hydrolase is missing/defective

  
  

  • ex: Gaucher’s or Tay-Sachs