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MBB 231 > lec 8- vesicular trafficking > Flashcards

lec 8- vesicular trafficking Flashcards

1
Q

what does the Cis Golgi Network do (CGN)?

A

functions to sort proteins for the ER or the next golgi station

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2
Q

what does medial cisternae do?

A

it is where processing takes place in the golgi

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3
Q

what does the trans golgi network do (TGN)?

A

functions in sorting proteins either to the membrane or various intracellular destinations

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4
Q

what gets processed in the golgi?

A

the N-linked oligosaccharide that was added to nearly every protein in the ER

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5
Q

what is not as abundant as N-linked glycoproteins?

A

O-linked glycoproteins, attached to a serine or threonine hydroxyl, they are abundant in extra cellular matrix

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6
Q

what does the glycostation do?

A

-participates in sorting in the trans golgi network
-limits flexibility of protruding oligosaccharide that can prevent others from arriving to protein surface
-make glycoproteins more resistant
-serves as recognition molecule in cell-cell interactions
bottom line: gives a cell the ability to generate many chemically distinct molecules at the cell surface

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7
Q

what is vesicular transport model and cisternal maturation model?

A

-cargo is shuttled from CGN to TGN

-each cistern matures as it moves from CGN to TGN

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8
Q

what are the functions of coated vesicles?

A

-cause the membrane to curve and form a vesicle
-select the components to be carried by vesicle

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9
Q

what is COPII-coated vesicles?

A
  • move materials from ER “forward” to the VTC in the ERGIC and the golgi complex
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10
Q

what is COPI-coated vesicles?

A

move materials from VTC in the ERGIC and from the Golgi complex “backward” to ER or from trans golgi to cis golgi

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11
Q

what is VTC and ERGIC?

A

VTC: vesicular tubular cluster, located in endoplasmic reticulum golgi intermedidiate compartment (ERGIC)
ERGIC: is an organelle involved in mediating traffic between ER and golgi

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12
Q

what do coat proteins do?

A

involved in endomembrane transport

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13
Q

what do V-snare proteins do?

A

it is a recognizing protein

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14
Q

what sequence do soluble resident ER proteins have?

A

KDEL (Lys-Asp-Glu-Leu), tell the golgi that this protein must remain in the ER

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15
Q

what happens to the KDEL protein when it gets to the golgi?

A

-the KDEL sequence binds to a KDEL receptor, which facilitiates COPI to take the KDEL protein back to the ER

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16
Q

how does vesicle budding begin?

A

budding begins with the recruitment of a small GTP- membrane following by binding of cytosolic coat proteins to the cytosolic domain of membrane cargo proteins

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17
Q

what may membrane cargo proteins be?

A

transmembrane proteins or receptor proteins that bind soluble proteins for transport

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18
Q

what do snare proteins do?

A

involved in the fusion of biological membranes

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19
Q

where are v-snare and t-snare proteins?

A

v-snare is in the vesicle and t-snare is in the target membrane, bringing them together to fuse

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20
Q

what are synaptobrevin and syntaxin?

A

synaptobrevin is a V-snare in the synaptic vesicle, syntaxin is a T-snare apart of the membrane of the nerve cell

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21
Q

how does botox paralyze muscles?

A

inhibits snare pairs from forming (synpatobrevin and syntaxin)

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22
Q

what do clatherin coated vesicles do?

A

clatherin coated vesicles are involved in transport from trans-golgi network to lysosomes and plasma membrane and vice versa

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23
Q

what is clatherin?

A

major protein component of clatherin coated vesicles

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24
Q

what is triskelion?

A

a clatherin molecule, each clatherin molecule consists of three large and three small polypeptide chains

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25
Q

how many enzymes do lysosomes have?

A

50 enzymes produced in the RER and can hydrolyze virtually all biological macromolecules

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26
Q

at what pH do lysosome enzymes function the best at in the lumen?

A

pH = 4.6

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27
Q

what do the transport proteins in the lysosome do?

A

carry products of macromolecule digestion to the cytosol for reuse

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28
Q

what is utilized for sorting and transporting lysosomial enzymes?

A

clatherin-coating vesicles

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29
Q

where are lysosomial proteins tagged and with what?

A

in the cis-golgi with phosphorylated mannose residues

30
Q

what recognizes the tagged lysosomial proteins?

A

mannose-6-phosphate receptors which are bound by coat proteins in the TGN

31
Q

what are lysosomial enzymes from the TGN transported in?

A

clatherin-coated proteins

32
Q

what do the coats of clatherin coated proteins contain?

A
  1. an outer lattice composed of clatherin
  2. an inner shell composed of GGA adaptor proteins
  3. the G-protein Arf1-GTP, used to initiate membrane curvature and recruit adaptors
33
Q

what does the phosphotase do to M6P (mannose-6-phosphate) residues?

A

removes the phosphate to prevent rebinding to M6P receptors

34
Q

how are early endosomes generated?

A

generated by receptor mediated endocytosis

35
Q

what do early endosomes fuse with and what occurs?

A

with late endosomes which then either transition to a lysosome or fuses with existing lysosomes (more likely)

36
Q

what is autophagy?

A

a process of lysosomes that is a pathway that allows cytosolic proteins and organelles to be delivered to the lysosomial interior for degredation

37
Q

what is a phagophore?

A

a double membrane structure that envelops an organelle to produce-membrane sequestering vesicle called an autophagosome and the enclosed contents are degraded

38
Q

what causes lysosome storage diseases?

A

caused by deficiency of a lysosomal enzyme which results in accumulation of material in the lysosome

39
Q

what are the symptoms of lysosomial diseases?

A

can be either severe or barely detectable

40
Q

what causes severe lysosomial diseases?

A

mutations in lysosomial membrane proteins that impair transport of substances from lysosomial lumen to cytosol

41
Q

what is type II glycogenosis?

A

a disease where glycogen accumulates in the liver, heart or skeletal muscles

42
Q

what causes type II glycogenosis?

A

glycogen is degraded by lysosome enzymes known as alpha-1-4-glycosidase, if enzyme is not present accumulation will occur

43
Q

what is Tay-Sachs disease?

A

an accumulation in nervous tissue of gangliosides as a result of the absence of a particular lysosomial enzyme

44
Q

what is done to add the corrective lysosomial enzyme back?

A

enzyme replacement therapy

45
Q

what is used to treat gauchers disease?

A

cerezyme, a modified glucocerebrosidase recognized by mannose receptors on the surface of cells for uptake

46
Q

what is done to inhibit the synthesis of materials that accumulate?

A

substrate reduction therapy

47
Q

what is used to treat both gaucher and niemann-pick disease?

A

Miglustat

48
Q

what are the steps that occur between vesicle budding and vesicle fusion?

A
  1. movement of vesicle toward target compartment, mediated largely by microtubules and their motor proteins
  2. tethering vesicles to the target compartment, mediated by a diverse collection of tethering proteins
  3. docking vesicles to the target compartment, vesicle and target compartment membranes come into close contact via interaction between integral proteins and the two proteins
  4. fusion between vesicle and target membranes
49
Q

what is exocytosis?

A

discharge of a secretory vesicle or granule after fusion with plasma membrane, triggered by Ca2+

50
Q

what forms fusion pores?

A

interactions between vesicle and plasma membranes

51
Q

what part of vesicle becomes outer and inner part of Plasma Membrane?

A

lumen and cytosolic part

52
Q

what is endocytosis?

A

a process by which the cell internalizes cell-surface receptors and bound extracellular ligands

53
Q

what are the two categories of endocytosis?

A

bulk phase and receptor mediated

54
Q

what is bulk phase endocytosis?

A

the nonspecific uptake of extracellular fluids and may function primarily in the recycling of membrane between the cell-surface and interior compartments

55
Q

what is receptor mediated endocytosis (RME)?

A

brings about uptake of specific ligands following their binding to receptors on the external surface of the plasma membrane

56
Q

what is transcytosis?

A

a combination of exo and endocytosis

57
Q

what is the receptors in RME concentrated in?

A

concentrated in coated pits at 10-20 times their level in the plasma membrane

58
Q

what becomes bound to coated pits?

A

substances that enter the cell via clatherin mediated RME

59
Q

what happens to clatherin coated regions?

A

invaginate into the cytoplasm and then pinch free of the cytoplasm

60
Q

what do coated vesicles contain between the clatherin lattice and the surface of the vesicle?

A

adaptors such as AP2

61
Q

what do AP2 adaptors contain?

A

multiple subunits that have different functions

62
Q

what do AP2 adaptors do?

A

engage cytoplasmic tails of specific receptors to select bound cargo molecules, and bind and recruit the molecules of the overlying lattice

63
Q

what forms a dynamic network of molecules in coated vesicles?

A

accessory proteins

64
Q

what do accessory proteins do?

A

cargo recruitment, coat assembly, membrane bending and invagination, interaction wiht cytoskeletal components, vesicle release, and membrane uncoating

65
Q

what is Dynamin and what does it self assemble into?

A

a G protein required for the release of clatherin coated vesicles from the membrane where it forms, self assembles into helical collar around neck of an invaginated coated pit, uses GTP to provide mechanical force

66
Q

what does dynamin promote?

A

a GTP-mediated fission of the coated pit from the plasma membrane followed by disassembly of the dynamin ring

67
Q

what are low density lipoproteins (LDL)

A

a complex of cholesterol and proteins, has 1500 cholesterol molecules surrounded by monolayer of p-lipids and cholesterol and a single molecule of the protein apolipoprotein B which interacts with LDL receptor

68
Q

what happens to LDLs?

A

taken up by RME and then to lysosome to release cholesterol

69
Q

what drugs lowers LDL levels?

A

statins which blocks HMG CoA reductase, an enzyme used in synthesis of cholesterol

70
Q

how much time does it take a LDL receptor to make a round?

A

10 to 20 minutes

MBB 231 (17 decks)

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