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Molecular 2018 > Lecture 18 > Flashcards

Lecture 18 Flashcards

1
Q

What do proteases, nucleases, glycosidases, lipases, phopholipases, phosphatases, and sulfatases all have in common?

A

they are all different types of lysozomes (acid hydrolases)

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2
Q

Describe the conditions for optimal activation of a lysosome.

A

an acidic environment and proteolytic cleavage

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3
Q

What is vacuolar ATPase pumps on lysosomes?

A

They pump H+ into lysosomes in order to maintain the acidic pH within their membrane and to drive the transport of small metabolites across the lysosomal membrane

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4
Q

True or false

lysosomes are homogenous

A

False

they are heterogenous and derived from late endosomes

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5
Q

Explain the role of late endosomes and endolysosomes when it comes to the maturation process of a lysosome

A

late endosomes fuse with prexisting endolysosomes or lysosomes (after the digestion of their contents by hydrolase) to form a mature lysosome.

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6
Q

List the 3 “lines of trafficking” that eventually end up fusing with lysosomes

A

Phagocytosis forming phagosomes

Endocytosis forming late endosomes

Autophagy forming autosomes

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7
Q

Describe autophagy. what type of trafficking vesicle is formed during autophagy?

A

means “self eating” and occurs via the formation of vesicular bodies within the cell

these vesicular bodies merge with one another and engulf the organelle/material that is destined for lysosomal digestion into an “autophagosome”

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8
Q

Describe how membrane proteins and hydrolases are transported to lysosomes.

A

lysosomal enzymes are co-transitionally transported into the rough ER, then to the golgi network (leave via the TGN), and then bud off into endosomes

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9
Q

How are lysosomal proteins sorted?

A

Lysosomal hydrolases have mannose-6-phosphate (M6P) added to them in the CGN

The receptors in the TGN recognize the M6P sugar, a phosphate is added, and they are packaged into clathrin coated vesicles, headed for mature lysosomes

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10
Q

during the synthesis of lysosome precursor enzymes, what all is added in the CGN?

A

P-GlcNAc and M6P sugar (which is uncovered in the TGN)

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11
Q

once a transport vesicle fuses with a mature lysosome, what happens?

A

a phosphate is removed from the complex and the lysosomal hydrolase precursor dissociates from the M6P receptor due to the high pH

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12
Q

after delivering the hydrolase to a lysosome, what happens to M6P receptors?

A

they are sent back to the golgi in a “receptor retrieval” vesicle

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13
Q

How is the UDP-GlcNAc added to a lysosomal hydrolase? where/how is it added?

A

GlcNAc phosphotransferase adds the UDP-GlcNAc to the N-linked oligosaccharide (which has a terminal M6P residue)

UMP is lost during the first step of this process

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14
Q

After a lysosomal hydrolase is released from GlnNAc phosphotransferase, what happens?

A

GlcNAc is removed

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15
Q

describe GlcNAc phosphotransferase in terms of it’s sites

A

it has a catalytic site where it adds UDP-GlcNAc to the lysosomal hydrolase

it has ha recognition site that recognizes the signal patch of a lysosomal hydrolase

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16
Q

generally describe lysosomal storage diseases

A

they are genetic defects in lysosomal hydrolases that cause the accumulation of undigested material in lysosomes

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17
Q

List 2 lysosomal storage diseases and describe them

A

Hurler’s disease: mutation in the enzyme required to breakdown glycoaminoglycans

Inclusion cell disease: all of the lysosomal hydrolases are missing and undigested substrates accumulate as “inclusions”

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18
Q

What happens there is a defective/missing GlcNAc phosphotransferase?

A

M6P is not added to lysosomal hydrolases which causes enzymes not getting phosphorylated

Without being phosphorylated they are not sorted into vesicles and trafficked to lysosomes

19
Q

What is endocytosis? what are the 2 types of endocytosis?

A

the uptake of macromolecules form the exterior of the cell

Phagocytosis and pinocytosis

20
Q

describe the relationship between endolysosomes and lysosomes

A

existing lysosomes fuse with endolysosomes in order to create more mature lysosomes. this process occurs repeatedly

21
Q

What is the main difference between phagocytosis and pinocytosis?

A

the size of the particle(s) being endocytosed

large=phagocytosis
small=pinocytosis

22
Q

Describe the process of receptor-mediated endocytosis.

A

select molecules bind to receptors on the outside of the membrane and accumulate in clathrin coated pits

23
Q

give an example of receptor-mediated endocytosis and what happens when this pathway is blocked.

A

cholesterol uptake is an example

atherosclerosis occurs if this pathway is blocked

24
Q

describe how receptor-mediated endocytosis yields free cholesterol on the inside of the cell

A

LDL’s bind to receptors on the outside of the membrane and accumulate in clathrin-coated pits

these form coated vesicles that fuse with early endosomes, destines for lysosomes

hydrolytic enzymes digest the LDL into free cholesterol and receptors in the endosome return to the PM

25
Q

are clatherin coated vesicles altered in any way before they fuse with the endosome? explain

A

yes, their clathrin coat is removed

26
Q

what is the result of defective coated-pit-binding-sites?

A

cardiovascular disease, because you cannot properly absorb cholesterol/LDL into the cell

27
Q

what are the 3 possible fates of endocytosed receptor proteins?

A

recycling them back into the PM

transcytosis across the cell cytoplasm

degradation in the endolysosome

28
Q

why would a vesicle be ubiquitinated?

A

ubiquitination signals for a vesicle to be degraded by a lysosome

29
Q

what is special about transporters in specialized recycling endosomes?

A

they will not be activated and transported to the PM unless they are signalled

insulin signalling GLUT to transport glucose across the membrane is an example of this

30
Q

Describe what WBC’s are involved in phagocytosis, what type of material is ingested during phagocytosis, and what happens to the undigested material

A

Macrophages and neutrophils

invading microorganisms, senescent cells are scavenged, and apoptotic cells

it is exocytosed

31
Q

When antibodies bind to a microbe, what is recognized by macrophages/neutrophils?

A

The Fc chain is recognized by the Fc receptor on the surface of macrophages/neutrophils

32
Q

what controls pseudopod formation during phagocytosis? what is polymerized to form pseudopods?

A

Rho GTPases and phosphoinositide signaling

Actin

33
Q

What triggers phagocytosis?

A

it is a cargo-triggered process

34
Q

Describe pinocytosis

A

it is “cell drinking” that is constantly occurring

ingests small pieces of the PM in the form of vesicular pits (that have some extracellular fluid trapped in them)

35
Q

What are caveolae? what are they “enriched in”?

A

flask-shaped invaginations in the PM involved in pinocytosis

they are enriched in cholesterol, GPI-anchored membrane proteins, and glycosphingolipids

36
Q

how do caveolae invaginate? do they connect with lysosomes?

A

they invaginate via their lipid composition, NOT by the protein coat (pinched off by dynamin and form caveosomes)

No, they do not connect with lysosomes

37
Q

During exocytosis, where do vesicles get transported? what are the 2 different types of exocytosis?

A

from the TGN to the PM

Constitutive and regulated

38
Q

Compare the Constitutive and regulated exocytosis pathways

A

Constitutive: operates continuously and is used to put newly synthesized PM lipids into the PM

Regulated: triggered by signals and is used to release hormones/neurotransmitters

39
Q

When secretory vesicles are being formed, how is the selected protein concentrated in the vesicle?

A

retrieval of all the other proteins that are not selected for that specific secretory vesicle leads to concentration of the specific protein in the vesicle.

40
Q

What does the TGN promote in secretory proteins?

A

Proteolytic processing

41
Q

v-SNARE and t-SNARE in synaptic vesicles are called what?

A

v-SNARE: synaptobrevin

t-SNARE: syntaxin

42
Q

Describe the process of exocytosis of synaptic vesicles

A

Docking: triggered when a Ca2+ sensing protein has Ca2+ bound to it.

Priming I: SNARES begin to complex, however complexin interrupts

PrimingII: complexin is removed after Ca2+ interacts

Fusion: SNAREs fully complex, fusion pore opens, and Ca2+/Complexin dissociate

43
Q

What is the organelle that sits nearby synapses and helps create/recycle synaptic vesicles?

A

the endosome

44
Q

t-SNARE (syntaxin OR SNAP 25) is a snare type that is only involved in what type of vesicle fusion? explain how it is involved

A

the vesicle fusion that occurs when exocytosing synaptic vesicles into the synaptic cleft

syntaxin and SNAP 25 are 2 different types of t-SNAREs that complex with the v-SNARE of the synaptic vesicle

Molecular 2018 (39 decks)

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