5.1 Vesicular Transport II: Trans Golgi Flashcards

1
Q

What are the three major export pathways from the trans golgi?

A

Signal mediated diversion: 1) trans golgi to lysosomes and 2) from trans golgi to secretory vesicles

Constitutive secretory pathway: 3) trans gogli to the cell membrane

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2
Q

How is the movement of vesicles through each pathway directed?

A

by specific signaling molecules found on the surface of the vesicles.

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3
Q

How is the movement of proteins into each vesicle type regulated?

A

by mechanisms that are specific to each secretory pathway.

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4
Q

What type of proteins are moved into lysosomes?

A

digestive enzymes = acid hydrolases

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5
Q

How are digestive enzymes (acid hydrolases) targeted to lysosomes?

A

by addition of mannose-6-phosphate (M6P)

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6
Q

How is mannose-6-phosphate added to lysosomal hydrolase?

A

two enzymes are needed to add the M6P.

Nucleic acid uracil (UPP-GlcNac_
GlcNAc Phosphotransferase

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7
Q

What happens if there’s a mutation on either one of the two enzymes needed to attach mannose 6 phosphate to lysosomal hydrolase?

A

it can cause a number of human disease problems linked to the inability of lysosome to function properly

ex: in lysosomal storage diseases, undigested material accumulates in lysosomes causing pathogenesis in the nervous system.

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8
Q

What happens in I Cell diseases?

A

lysosomal hydrolases are excreted to the cell exterior

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9
Q

Where does the phosphorylation of mannose occr?

A

w/in the central area of the gogli apparatus

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10
Q

What is the pathways taken by proteins modified by M6P signal?

A

1) protein moves to trans face and it is recognized by transmembrane M6P receptor. Receptor participates in the formation of clathrin coated vesicles which are targeted to vesicles in the lysosomal pathway.
3) the acidic interior of endosomal vesicle strips the phosphate group of the mannose and releases to targeted protein into the lysosome
4) empty receptor recycled back to trans gogli by retromer coated vesicles.

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11
Q

What transports empty M6P receptor back to trans gogli?

A

retromer coated vesicle.

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12
Q

What two types of mechanisms are there for endocytosis?

A

phagocytosis

pinocytosis

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13
Q

What is the difference between phagocytosis and pinocytosis?

A

Both bring material INTO the cell. (CELL EATING)
Phago brings in large particles and pino brings smaller things into cell including droplets of extracellular fluid and activated membrane receptors

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14
Q

The entry of cholesterol into cells is an example of what?

A

endocytosis

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15
Q

What is low density lipoprotein (LDL)? the organization

A

it is an organizing protein that helps cholesterol organize into small droplets by interaction w/phospholipids. An LDL receptor at the plasma membrane binds LDL particles that are in the extracellular environment and then recruits adaptor molecules which link clathrin on the cytoplasmi side of the membrane to LDL particle

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16
Q

How is clathrin linked to LDL particles on the cytoplasmic side of the membrane.

A

An LDL receptor at the plasma membrane binds LDL particles that are in the extracellular environment and then recruits adaptor molecules which link clathrin on the cytoplasmic side of the membrane to LDL particle.

Adaptor molecule links them

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17
Q

What is formed as clathrin molecules w/bound receptor and LDL particles assemble together?

A

they form a coated pit, which assembles large numbers of LDL particles before budding off a completed endosomal vesicle.

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18
Q

Why are coated pits important in endocytosis of cholesterol?

A

they allow cells to concentrate molecules b/4 bringing them into the cell and allows efficient uptake of molecules from extracellular space.

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19
Q

What is the fate of the LDL particle and receptor as they enter the cell?

A

LDL particles and receptor start together but take different paths. They both end up in early endosome but due to pH levels vesicle and particle separate. Membrane vesicles w/receptors bud off of the transport vesicles and return to the plasma membrane to be used again.

Early endosome merges with lysosome to form secondary endosomes and this is where LDL particles are digested causing the release of cholesterol

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20
Q

What happens to the clathrin coat after entering the cytoplasm?

A

clathrin coat dissociates from the vesicle in a process called uncoating.

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21
Q

How are early endosomes formed?

A

from the uncoating of clathrin from vesicles and vesicle free of clathrin fuses with endosome to form early endosomes.

22
Q

What does the low pH levels inside endosomes do to LDL particles and LDL receptors?

A

causes them to dissociate

23
Q

What happens to LDL receptors after dissociating w/LDL particles in the endosome?

A

membrane vesicles will bud off the endosome and recycle the receptor back to the plasma membrane for reuse.

24
Q

How are secondary lysosomes formed?

A

late endosomes fuse w/lysosomes

25
Q

How is cholesterol molecule released inside the cell?

A

LDL particles are digested w/in the secondary lysosome and this releases cholesterol to be used by cells.

26
Q

In addition to degrading the contents of endosomes, what else do lysosomes degrade?

A

they handle the degradation of proteins associated with the plasma membrane

27
Q

How do lysosomes degrade proteins associated with the plasma membrane?

A

1) early endosomes undergo membrane internalization rearrangements
2) this leads to formation of internal membrane compartment called multi-vesicular bodies
3) transmembrane proteins such as cell surface receptors are targeted to these bodies by umbiquintination of their cytoplasmic extensions
4) umbiquidation is detected by a series of proteins called escort or ESCRT proteins.

28
Q

What are the roles of ESCRT 0, I, II, and III?

A

hand of ubiquinated membrane receptors until they’re deposited into an invagination of an endosomal membrane.

29
Q

What is the opposite of endocytosis?

A

exocytosis aka secretion.

30
Q

How can exocytosis occur?

A

occurs through two distinct pathways

1) constitutively active
2) temporary storage followed by release when some signal is received

31
Q

Which exocytosis pathway is regulated? Which one is unregulated?

A

Constitutive is continous and unregulated

secretory vesicles is regulated since they need a signal to release their contents.

32
Q

What types of signal regulate secretory vesicles? AKA What is needed for these vesicles to release contents?

A

Ca2+ and cAMP

33
Q

What are signaling patches?

A

areas of membrane specialization containing receptors for secreted proteins and co-proteins

34
Q

How do immature vesicles mature?

A

signaling patches
removal of some of the membrane (lead to further concentration of secreted proteins)
removal of fluid interior by clathrin coated vesicles

35
Q

What type of membrane associated proteins are found on secretory vesicles?

A

SNARE family of protiens

36
Q

What do SNARE proteins do on secretory vesicles?

A

some are involved in membrane fusion with the plasma membrane and others regulate the fusion process

37
Q

How is protein secretion regulated?

A

dependent on the type of stimulation and amount of stimulation

ex:mast cell releasing histamine

38
Q

Phagocytosis is carried out by what tow specialized cells in our bodies?

A

1) macrophages

2) neutrophils

39
Q

What is the difference between macrophages and neutrophils?

A

macrophages consume dead or dying cells that originate in our own bodies such as old red blood cells

neutrophils (aka white blood cells) are first in line of defence against bacterial infection

40
Q

What is phagocytosis?

A

a special form of endocytosis that results in the internalization of large sstructures such as whole cells & bacteria.

requires reorganization of the cytoskeleton.

no coat proteins. Need a pseudopod made by actin polymerization to surround bacterio or othe cells.

41
Q

What is actin cytoskeleton?

A

creates membrane protrusions called psuedopods which assist in reorganization of the structural componets of cells being phagocitized.

42
Q

How is phagocytosis regulated?

A

by several signaling pathways

1) a GTPase called rho
2) lipids

43
Q

How are pseudopods formd?

A

Requires the presences of signaling lipids PIP2 and the phosphorylation of PIP2 by PI-3 Kinase is required for the closure of pseudopods around an object.

44
Q

lysosomes are often the destination of what kind of vesicles?

A

vesicles entering the cell through endocytosis

45
Q

How are multi-vesicular bodies formed? and for what purpose?

A

formed by early endosomes that undergo membrane internalization/rearrangement

Why?-to degrade transmembrane proteins like cell surface receptors

46
Q

how are transmembrane proteins targeted to multi-vesicular bodies?

A

by ubiquintination of their cytoplasmic extensions

ubiquidation is detected by a series of proteins called ESCRT

47
Q

How is phosphate donated to M6P to transport acid hydrolase to a lysosome?

A

The donor is the nucleic acid uracil with two phosphates attaching it to an N-acetylated
glucose

48
Q

How is phosphorylated N-acetyl glucose is added to lysosomal enzymes?

A

by an enzyme called N-acetyl glucose transferase that is abbreviated GlcNAc. It recognizes a signaling patch encoded into the sequence of the lysosomal enzyme and then transfers phospho-N-acetyl glucose to the terminal mannose sugar found on oligosaccharides attached to the lysosomal enzyme.

49
Q

When delivering lipids to the cell surface often times remodeling of the plasma membrane is necessary, what are examples of this? and what balances this act?

A
  • Cleavage furrow
  • Wound repair
  • phagocytosis

and endocytosis balances this

50
Q

How are pseudopods created?

A

he initial formation of a pseudopod requires the presence of the signaling lipid PIP2 and the phosphorylation of PIP2 by PI-3 kinase is required for the closure of psedopods
around an object