Lecture 14 Vesicular Transport II Flashcards

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1
Q

what are the membrane compartments of lysosome filled with

A

hydrolytic enzymes

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2
Q

what is the function of lysosomes

A

intracellular digestion of macromolecules

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3
Q

what type of enzymes are found in lysosomes

A
proteases 
nucleases
gylcosidases
lipases
phospholipase
phosphates
sullfatases
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4
Q

what do lysosomes require for optimal activation

A

acidic environment

proteolytic cleavage

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5
Q

vacuolar ATPase

A

pumps H+ into lysosomes to maintain acidic pH and drive transport of small metabolites

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6
Q

what does the Trans-Golgi network deliver to lysosomes

A

membrane proteins and hydrolyses

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7
Q

steps in co-translation transport of membrane proteins and hyrolases to lysosome in TGN

A

into rough Er

then transported via Golgi comes to TGN

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8
Q

TGN buds off Golgi to form

A

endosomes

these develop into lysosomes

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9
Q

what do lysosomal hydrolyses have that attach them in the CGN

A

sorting signal

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10
Q

sorting signal of lysosomal hydrolyses

A

Mannose 6 Phosphate

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11
Q

what do M6P receptors in TGN recognize

A

sorting signal sugar, M6P

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12
Q

after hydrolyses bind to TGN…

A

they are packaged into clathrin coated vesicles that bud off and delivered to endosomes then lysosomes

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13
Q

steps of lysosomal protein sorting

transport of newly synthesized lysosomal hydrolases to lysosomes

A
  1. on cis-Golgi mannose binds to hydrolase from ER and phosphate is added – becomes M6P
  2. M6P signal is uncovered as it moves thru Golgi
  3. M6P binds to M6P receptor, gets clathrin coated and buds off
  4. Transport to endosome, fusion with endosome
  5. hydrolyses dissociate from M6P receptors (due to low pH)
  6. Empty transports are recycled back to the TGN
  7. in endosomes, phosphate is removed and hydrolyses are kept in the endosome
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14
Q

what is the enzyme responsible for recognizing the lysosomal hydrolase?

A

GlCNAc phosphotransferase

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15
Q

how does the lysosome recognize the hydrolase

A

signal patch binds to the phsphotransferase

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16
Q

binding site of phosphotransferase binds

A

high mannose N-linked oligosaccharides

UDP-GLCNAc

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17
Q

steps in lysosomal recognition

A
  1. binding of signal path to recognition site of phosphotransferase
  2. transfer of GlcNAc-P to mannose at catalytic site
  3. release
  4. remold of GLcNAc
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18
Q

lysosomal storage disease

A

caused by genetic defects in lysosomal hydrolyses

results in accumulation of undigested material in lysosome

Inclusion Cell disease
Hurlers Disease
Missing GlcNAc phosphtransferase

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19
Q

Hurlers disease

A

mutation in the enzyme required to break down glycosaminoglycan chains

lysosomal storage disease

20
Q

Inclusion Cell Disease

A

missing hydrolyses in cell types

substrates accumulate as inclusions

21
Q

missing GlcNAc phosphotransferases cause

A

enzymes that aren’t phosphorylated and therefore not sorted into vesicles and delivered into lysosomes but instead are carried to cell surface and found in blood

22
Q

transport mechanisms in this lecture

A
  1. Transport from TGN to Lysosomes
  2. endocytosis
  3. exocytosis
23
Q

endocytosis

A

uptake of macromolecules from exterior across plasma membrane

24
Q

pinocytosis

A

form of endocytosis

small particles are ingested by pinocytic vesicles

25
Q

phagocytosis

A

form of endocytosis

large particles are ingested by phagosomes

26
Q

receptor mediated endocytosis

A

used to import macromolecules from outside cells

molecules bind to receptors on membrane surface then accumulate in clathrin coated pits

provides selective concentration mechanisms

27
Q

what is an example of receptor mediated endocytosis

A

cholesterol uptake

blockage of this pathway results in atherosclerosis

28
Q

role of clathrin coated pits in receptor mediated endocytosis

A

LDL receptors associate with clathrin-coated pits that then pinch off, carrying LDL particles and receptors

LDL particles are freed into extracellular space when clathrin is removed

29
Q

steps of cholesterol uptake

A
  1. endocytosis
  2. uncaring
  3. fusion with endosome
  4. budding off of transport vesicles
  5. return of LDL receptors to plasma membrane
30
Q

sequestering of endocytose proteins

A
  1. covalent modification with ubiquitin– requires only 1 ubiquitin
  2. ubiquitin tag facilitates the uptake of the receptors into endocytic vesicles
  3. ubiquitin is recognized by proteins that mediate the sorting process into the internal membrane vesicles of multi vesicular bodies

Lipid kinase helps regulate by phosphorylating phosphatidylinositol

serve as docking sites for the proteins that mediate the invagination proces

31
Q

possible fates of endocytose receptor proteins

A
  1. recycled transport vesicles
  2. degradation by endolysosome
  3. transcytosis of transport vesicle
32
Q

what type of cells use phagocytosis?

A

macrophages and neutrophils

phagosomes

33
Q

macrophages and neutrophils use phagocytosis by

A

ingesting invading microorganisms to protect against infection

scavenge senescent and apoptotic cells

34
Q

mechanism of phagocytosis

ex. antibody interaction

A
  1. antibodies bind to microbe
  2. Fc chain recognized by Fc receptor on surface of WBC
  3. pseudopod is formed and engulfs particle to form phagosome
35
Q

what triggers phagocytosis?

A

binding of a particle to receptors on phagocyte surface

36
Q

formation of pseudopod is driven by:

A

localized actin polymerization and reorganization

37
Q

formation of pseudopod is controlled by

A

Rho GTPases

phosphoinostitide signaling

38
Q

pinocytosis

A

cells ingest bits of PM in form of small pinocytotic vesicles

begins at clathrin coated vesicle

extraceullar fluid is trapped with solutes as they invaginate

39
Q

flask shaped invaginations in PM

A

caveolae

40
Q

caveolae

A

enriched in cholesterol and glycosphingolipids

caveoloae ingavingate into membrane by lipid composition

don’t connect with lysosomes

41
Q

structural protein of caveolae

A

caveolin

42
Q

exocytosis

A

transport from TGN to cell exterior

fusion of vesicles with PM

43
Q

____ secretory pathway operates continuously

A

constitutive

44
Q

____ secretory pathway is triggered by signals

A

regulated

signal combines with secretory vesicle and it is fused with membrane

45
Q

three mechanisms of protein sorting in TGN

A
  1. signal mediated diversion to lysosomes
  2. signal mediated diversion to secretory vesicles
  3. constitutive secretory pathway
46
Q

formation of secretory vesicles

A

involves selective aggregation/clumping of proteins

TGN promotes proteolytic processing of the proteins

47
Q

steps in formation of synaptic vesicle

A

1, delivery of synaptic vesicle membrane components to presynaptic plasma membrane
2. endocytosis of synaptic vesicle membrane components to form new synaptic vesicles directly
3. endocytosis of synaptic vesicle membrane components \
and delivery to endosome
4. budding of synaptic from endosome
5. loading o fNeurotransmitter into synaptic vesicle
6. secret of Neurotransmitter by exocytosis