Advanced Cell biology - lecture 8 - lysosome: concepts and definitions

Question 1

The lysosome is responsible for the digestion of what?

Answer 1

Various macromolecules (acts as the cell’s garbage can)

Question 2

What type of enzymes does the lysosome contain?

Answer 2

Acid hydrolases

Question 3

What contributes to the lysosomes acid environment?

Answer 3

Vacuolar (or V-type) ATPase - pumps H+ into lysosome to maintain low pH

Question 4

Acid hydrolases are only functional at what pH?

Answer 4

4.5-5

Question 5

Lysosomes are fed through which pathways?

Answer 5

1) Endocytic (fusion of late endosome with lysosomes)
2) Phagocytosis pathway
3) Autophagy pathway

Question 6

Specialized lysosomes in plants are called ______. These control what?

Answer 6

Vacuoles and control pH and osmotic pressure

Question 7

Lysosome resident proteins are targeted to the lysosome via what?

Answer 7

M6P and M6P receptor

Question 8

Lysosomal enzymes are sent to the lysosome via which pathway?

Answer 8

The ER to Golgi to lysosome transport pathway (a branch of the secretory pathway)

Question 9

What is the purpose of the acid hydrolases only being active at low pH?

Answer 9

This ensures that these enzymes are only fully active in an intact, mature lysosome.

Question 10

What are the different acid hydrolases in the lysosome?

Answer 10

proteases, glycosidases, phosphatases, phospholipases, nucleases, lipases, sulfatases

Question 11

Lysosomal acid hydrolases and other lysosome resident proteins are given a specific N-linked oligosaccharide - ____ - in the ______.

Answer 11

1. M6P

2. Golgi

Question 12

M6PR proteins in the TGN package the hydrolases into ______-coated vesicles.

Answer 12

Clathrin

Question 13

The M6PR interacts with M6P at which pH? At which pH is it released?

Answer 13

The M6PR interacts with M6P at a pH of 6.5-6.7.

The M6P is released at a pH of 6.

Question 14

In what compartment is the pH 6 to allow release of M6P from the M6PR?

Answer 14

the early endosome

Question 15

In what compartment is the pH 6.5-6.7 to allow binding of M6P by the M6PR?

Answer 15

TGN

Question 16

What are the different lysosomal storage diseases (just the names)?

Answer 16

Hurler’s, Hunter’s, Pompe, I-cell disease (mucolipidosis type II) and others

Question 17

What is common in the LSDs (lysosomal storage disease) Hurler’s, Hunter’s, Pompe?

Answer 17

Single acid hydrolase missing resulting in accumulation of a specific macromolecule type in the lysosome.

Question 18

Missing a single acid hydrolase, as is the case in many LSDs, leads to what?

Answer 18

Accumulation of a specific macromolecule type in the lysosome which causes the lysosomes to become enlarged and appear as large inclusions, due to failure to digest incoming macromolecules.

Question 19

What is I-cell disease?

Answer 19

Most serious of the LSDs since almost all hydrolytic enzymes are missing from the lysosome.
These enzymes accumulate outside the cell.

Question 20

What causes I-cell disease?

Answer 20

GlcNac phosphotransferase gene is mutated and thus all lysosomal proteins fail to get delivered - default secretion.

Question 21

What are the different types of endocytosis?

Answer 21

1) Pinocytosis
2) Receptor mediated endocytosis
3) Phagocytosis

Question 22

Pinocytosis is performed by?

Answer 22

Performed at all times by all cell types.

Question 23

What is receptor-mediated endocytosis?

Answer 23

Endocytosis of receptors and their bound ligands.

Question 24

Phagocytosis is performed by what?

Answer 24

Macrophages, neutrophils and other professional scavengers.

Question 25

How is cholesterol taken into cells? (what type of endocytosis)

Answer 25

Receptor-mediated endocytosis

Question 26

Cholesterol is transported in the blood under what form?

Answer 26

LDL

Question 27

LDL binds to what?

Answer 27

LDL receptor on cell surface

Question 28

What portion of the LDL receptor is mono-ubiquitinated? What purpose does it serve?

Answer 28

The cytosolic tail of the receptor is monoubiquitinated (i.e. a ubiquitin protein is covalently attached). This acts as a signal for internalization by interacting with clathrin adaptor proteins.

Question 29

What occurs in familial hypercholesterolemia?

Answer 29

Heterozygous individual experiences partial failure to take up LDL. (thus there is too much cholesterol in the blood)

Question 30

The early endosome has a pH of ___, this causes _____ release from the LDL receptor.

Answer 30

1) 6

2) LDL

Question 31

What is the reason for the accumulation of cholesterol in the blood iin individuals heterozygous for hypercholesterolemia?

Answer 31

LDL receptor lacks part of cytosolic tail that normally is ubiquitinated. Thus, receptors cannot be internalized (since they cannot interact with the clathrin adaptor proteins). This leads to cholesterol accumulation in the blood.

Question 32

EGF binding to EGFR is a signal for what?

Answer 32

Signal for cell division and other change in cell behaviour.

Question 33

After signalling is induced by EGF binding to EGFR, both the ligand and receptor are _________. This causes what?

Answer 33

Destroyed. This downregulates the cell response to the signal.

Question 34

How are multivesicular bodies formed?

Answer 34

Vesicles from early endosomes fuse and migrate along MTs as multivesicular bodies.

Question 35

What does the multivesicular body fuse with?

Answer 35

Fuses with a late endosome or lysosome.

Question 36

In the ESCRT pathway, ESCRTs bind what?

Answer 36

Endosomal PIPs (in the cytosolic layer) and ubiquitin (monoubiquitin added to the cytosolic tail of the EGFR)

Question 37

In the pathway from early endosome to late endosome, what does ubiquitin act as?

Answer 37

1) Signal for the internalization of the receptor.

2) Acts as a signal to promote pinching off and sequestration of entire receptor within lysosome (ESCRT complex)

Question 38

Multiple ESCRT complexes function together to _________ ubiquitinated receptors into the lysosome.

Answer 38

sequester

Question 39

What is the result of the ESCRT pathway?

Answer 39

Membrane bound “vesicle” inside the endosome.

Question 40

The ESCRT pathways is used by some _______ viruses such as Ebola and HIV, to _____ the cell.

Answer 40

1) Enveloped

2) Exit

Question 41

The ESCRT pathway is also used in _________.

Answer 41

autophagy