Section 7E: Vesicle traffic to the lysosome

Question 1

What are lysosomes specialized in?

Answer 1

• they are specialized in breaking down proteins and material into their building blocks
• it converts the macromolecules back into building blocks that can be recycled

Question 2

Pathway from Golgi to lysosome

Answer 2

• Delivery of newly synthesized proteins and membrane from the golgi to the lysosome
• Certain proteins and membranes must be recycled back to the golgi

Question 3

What type of proteins go to the lysosome?

Answer 3

bad/poor proteins

Question 4

lysosomes digest macromolecules and lipids:

Answer 4

enriched in hydrolytic enzymes

Question 5

What prevents self digestion?

Answer 5

1. Hydrolytic enzymes are activated by:
   - proteolytic cleavage of inactivation sequence of amino acid - zymogens
   - acidic environment
2. Thus, hydrolases are inactive if leaked into cytosol
3. V-ATPase pump acidifies lysosomal lumen

Question 6

What is a V-type ATPase?

Answer 6

a type of pump protein that consumes ATP to transport protons across the lipid bilayer against the concentration gradient

Question 7

Why are hydrolytic enzymes important?

Answer 7

because the V-type ATPase pumps protons into the lumen (the interior of the lysosome) which lowers the pH of the lysosome to ~5

Question 8

At what pH do hydrolytic enzymes work

Answer 8

~ pH 5

Question 9

Four vesicle traffic routes converge on lysosomes

Answer 9

1. Golgi to late endosome: biosynthetic pathway
2. endocytosis
3. phagocytosis
4. autophagocytosis

Question 10

Golgi to late endosome

Answer 10

biosynthetic pathway delivers new hydrolytic and lysosomal proteins

Question 11

Endocytosis

Answer 11

delivers solute and membrane-bound extracellular and plasma membrane cargo for degradation

Question 12

Phagocytosis

Answer 12

delivers extracellular particles for degradation, like bacteria

Question 13

Autophagocytosis

Answer 13

delivers cell parts like damaged organelles for degradation

Question 14

How do lysosomal hydrolases go form golgi to the lysosome?

Answer 14

• Mannose-6-phosphate marks lysosomal proteins
• Mannose-6-phosphate is a unique sugar that is covalently attached to the end of a polysaccharide that is covalently attached to lysosomal hydrolases
• this Mannose-6-phosphate modifocation is a “sorting signal” for proteins to sort from the golgi to the lysosome via the “biosynthetic route”

Question 15

What is Mannose-6-phosphate ?

Answer 15

Mannose-6-phosphate is a unique sugar that is covalently attached to the end of a polysaccharide that is covalently attached to lysosomal hydrolases

Question 16

What is the M6P receptor?

Answer 16

• Mannose-6-phosphate receptor
• a protein an integral membrane protein that is able to have a ligand binding side that faces the interior of the golgi
• its job is to use this ligand binding site to bind to any protein that has Mannose-6-phosphate (which are lysosomal hydrolases)

Question 17

What happens after M6P receptor is bound to Mannose-6-phosphate?

Answer 17

• it gets packaged into a vesicle made by a clathrin coat in the golgi
• these vesicles are then able to be delivered into the lysosome
• they fuse with the lysosome where they deliver their contents
• the retrieval arm then brings the M6P receptors and forms vesicles with the empty M6P receptors and delivers them back to the golgi to continue this constant cycle

Question 18

Endocytosis, Phagocytosis, Autophagocytosis

Answer 18

all deliver macromolecules that will be broken down into subunits

Question 19

The biosynthetic pathway

Answer 19

delivers hydrolase enzymes to the lysosome from the golgi