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M2M Exam 3 wk 2 > Secretory Pathway I & II > Flashcards

Secretory Pathway I & II Flashcards

1
Q

Proteins move through _____ across a membrane from cytosol in an organelle

A

translocators

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2
Q

Steps of transmembrane transport to the ER

A
  1. peptide synthesis is initiated on ribosome in the cytoplasm
  2. signal sequence is reached during synthesis that signals for the translocation of the growing peptide in the ER
  3. a signal recognition particle (SRP) binds the translated signal sequence and free ribosome
  4. SRP then binds GTP and halts elongation of peptide
  5. Ribosome and peptide are brought the SRP receptors on the cytosolic face of the ER
  6. The growing peptide is transferred to a translocon complex
  7. SRP dissociated from the complex as GTP is hydrolyzed
  8. Elongation of the peptide continues, feeding the growing peptide into the lumen of the ER
  9. After synthesis is complete, the signal sequence is cleaved by signal peptidase and the ribosome dissociates and is recycled
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3
Q

signal sequences vary, but all contain

A

8-15 hydrophobic residues

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4
Q

SRP as a

A

methionine rich binding pocket that allows it to be flexible in terms of what it binds

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5
Q

cargo proteins are released into

A

the lumen of the ER

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6
Q

Transmembrance proteins differ in that they

A

contain a transmembrane called the stop transfer sequence.

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7
Q

when the stop transfer sequence is reached during synthesis, the

A

growing peptide is moved from the translocon complex to the membrane, where its synthesis, as a transmembrane protein, continues

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8
Q

type 1 transmembrane proteins have their amino terminus

A

inside the lumen

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9
Q

type 2 transmembrane proteins have their amino terminus

A

outside the lumen

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10
Q

transmembrane proteins may have

A

more that one transmembrane domain

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11
Q

Proteins and lipids move from one compartment to another by

A

membrane bound transport intermediates

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12
Q

a vesicle forms through _____

A

exocytosis: a portion of the membrane of the ER or other compartment and its contents (transmembrane and cargo proteins) buds off

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13
Q

the vesicle is lined with a _____

A

a coat that is specific for the proteins it contains and the final destination of the bud

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14
Q

the vesicles is transported to its destination along

A

microtubules via motor proteins (dyenin and kinesin)

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15
Q

the vesicle sheds its coating and membrane fusion occurs via ____ proteins

A

via SNARE proteins

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16
Q

the contents of the vesicles are then released into the ____

A

lumen of the target compartment

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17
Q

List the major function of the ER

A
  1. synthesis of lipids
  2. control cholesterol homeostasis
  3. synthesis of proteins on membrane bound ribosomes
  4. Co-translational folding of proteins and early post translational modifications
  5. Quality control
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18
Q

synthesis of which lipids occurs in the ER?

A

phospholipid, ceramide and cholesterol

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19
Q

What is cotranslational translocation?

A

step in transmembrane transport where a peptide being made on a free ribosome is transported to a translocon in the membrane of the ER

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20
Q

synthesis of the growing peptide then ensues in the ______

A

translocon

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21
Q

name 3 well studied vesicle coats

A
  1. clathrin
  2. COPI
  3. COPII
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22
Q

Vesicle coats function is to _____

A

assist the membrane to change its shape in order to form a vesicle

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23
Q

how are different vesicular coats specific for cargo and transmembrane proteins? due to its variation in their shape and conformation,

A

because of its variation in their shape and conformation,

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24
Q

vesicular coats function to

A

target proteins to the correct final destination

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25
Q

clathrin function is t0 ____

A

transports proteins from the plasma membrane to lysosomes or back to the plasma membrane

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26
Q

COPI transports proteins from ___ to ____

A

transports proteins from Golgi to the ER

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27
Q

COPII transports proteins from ___ to ____

A

transports proteins from the ER to the Golgi

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28
Q

polyribosomes are located on

A

all on one mRNA

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29
Q

___ is the dominant organelle

A

ER

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30
Q

plasma cells function is ____

A

synthesizes and secretes anitbodies

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31
Q

Major Functions of the ER

A
  1. Synthesis of lipids (phospholipid, ceramide, and cholesterol)
  2. Control of cholesterol homeostasis (cholesterol sensor and synthesis)
  3. Ca+2 storage (rapid uptake and release)
  4. Synthesis of proteins on membrane bound
    ribosomes
    1. Co-translational folding of proteins and early post-translational modifications. 2. Post- translational insertion into the membrane
  6. Quality Control
32
Q

Integral membrane proteins: insertion into the ER membrane

Two mechanisms:

A
  1. cotranslational insertion (discovered 30 years ago) and

2. post- translational insertion (recently discovered).

33
Q

signal sequence binding pocket is lined by _____

A

methionines and is dry flexible

34
Q

How to move membrane

and cargo from one compartment to another?

A

Vesicle budding, translocation, and fusing are critical.

35
Q

ER soluble proteins

A

C terminal KDEL,

binds to KDEL receptor

36
Q

ER membrane proteins

A

C terminal KKXX,

binds to COPI coats

37
Q

Mannose 6-phosphate is a sorting signal for _____

A

sorting signal for lysosomal proteins

38
Q

Mannose 6-phosphate binds to a receptor that is targeted to ______

A

vesicles that fuse with the late endosome

39
Q

In the late endosome pH is ____ and the receptor and M6P tagged protein _____.

A

low

dissociate

40
Q

How are membrane proteins made with multiple TMDs?

A

These proteins have internal stop and start sequences. Some transporters and channels have many transmembrane domains. Most amino acid transporters have 12 TMDs, the CFTR (cystic fibrosis transmembrane conductance regulator) has 12 TMDs, and the voltage- gated sodium channel responsible for the neuronal and muscle action potential has 24 TMDs.

41
Q

vesicles move:

A

“forward” from the ER to the Golgi

and from the Golgi to the plasma membrane

42
Q

lysosome move:

A

“backward” moving vesicles

for retrieval.

43
Q

Describe the 3 mechanisms of protein transport

A
  1. gated transport
  2. Transmembrane transport:
  3. Vesicular transport: membrane-bound transport; requires adaptor and coat proteins.
44
Q

Gated transport:

A

requires a specific receptor protein to carry a folded protein from the cytosol into the nucleus through the pore complex.

45
Q

Transmembrane transport:

A

requires a translocator protein or protein complex (ie translocon) to move proteins across membrane.

46
Q

Vesicular transport:

A

membrane-bound transport; requires adaptor and coat proteins.

47
Q

Translocon:

A

Protein-conducting aqueous channel that spans the rough ER membrane.

48
Q

Protein sorting signals:

A

most proteins are “tagged” with a region (primary sequence or tertiary structure) that forms a “recognition patch”: this tells the cell how to package the protein and where to send it.

49
Q

there is a specific 5’ sequence that signals that the transcript is going to be pulled into the ER; if it’s absent,

A

the protein remains soluble in the cytosol.

50
Q

The 5’ sequence that signals ER translocations causes the ribosome translating that protein to

A

attach to the membrane of the ER (thus causing rough ER vs smooth ER).

51
Q

Co-translational translocation:

A

as mRNA is translated, it’s moved through the translocon into the ER lumen to be cleaved by signal peptidases and folded.

52
Q

The 5’ signal sequence binds to the ______; this opens the ________.

A

SRP (signal receptor particle) in the ER membrane

translocon and the nascent polypeptide is threaded through the translocon into the lumen as it’s translated (the 5’ signal sequence is cleaved off almost immediately so that it doesn’t make up a part of the final protein)

53
Q

SRPs:

A

have a multi-methionine “pocket” that binds to a wide variety of 5’ signal sequences.

54
Q

5’ signal sequences:

A

variable; often mainly nonpolar.

55
Q

Notice that the translocon is regulated on the______ as well by _______: Which means that it can:

A

luminal surface

binding protein BiP

expel proteins as well as admit them

56
Q

If the nascent protein is meant to be a membrane protein, the protein contains another region
(aside from the 5’ signal sequence) that interacts with the translocon:

A

a “stop-transfer sequence” which stops the transfer of the protein into the lumen– thus the protein remains “stuck” with a transmembrane domain in the ER membrane, one end of the protein in the lumen, and the other end of the protein in the cytosol. The “stuck” protein then translocates out of the translocon for further packaging.

57
Q

the positively charged end of the transmembrane domain winds up in the______ and the negatively charged end of the domain winds up in the ______

A

cytosol (outside the ER)

ER lumen.

58
Q

Asparagine-linked (N-linked) glycosylation:

A

as a polypeptide is threaded through the translocon, an enzyme (oligosaccharyl transferase) catalyzes the glycosylation of select asparagine residues in the protein (“core glycosylation”) with the motif N-X-S/T.

59
Q

Part of N-linked glycosylation involves trimming the

A

attached glycosyl groups to properly package the protein for transport to the Golgi apparatus.

60
Q

The_______ is what signals the ER that a protein is ready to be transported elsewhere.

A

trimming process

61
Q

List the major functions of the Golgi:

A
  1. Synthesis of complex sphingolipids from the ceramide backbone
  2. Additional post-translational modifications of proteins and lipids
  3. Proteolytic processing (protein cleavage)
  4. Sorting of proteins and lipids for Golgi compartments
  5. Morphology:
  6. How the Golgi apparatus transports proteins/lipids through itself:
    o Notice that N-linked glycosylation is finished in the Golgi: this, again, is a signal to move the protein to a new location
    o “Proproteins”: proteins that undergo proteolytic cleavage late in processing (Golgi).
    o One package sorting mechanism: by thickness of the package’s membrane (thicker -> plasma membrane; thinner stays in the ER membrane, that sort of thing).
62
Q

How does the Golgi apparatus transports proteins/lipids through itself?

A
  1. Depends on the type of things transported. Sometimes it’s by moving them from cisterna to cisterna with small vesicles; sometimes it’s by actually moving or modifying the entire cisterna that contains the material (“cisternal progression”).
  2. Which one used depends on the nature of the material– if it won’t fit inside a vesicle, tend to use cisternal progression.
63
Q

Vesicular “coats” are assembled at:

A

the site of vesicle formation:

64
Q

at the site of vesicle formation, what happens to the vesicular coats that are being assembled?

A

vesicular coats “sort” the proteins or lipids to be moved (different coat molecules “select” various types of cargo using adaptor proteins), and aid in pushing the vesicle out the side of the membrane.

65
Q

there are ______ in cargo:

A

adaptor binding motifs

66
Q

Cargo attracts a certain type of ______; the adaptor proteins then attract ____

A

adaptor protein

a certain type of coat.

67
Q

VAMP SNAREs are found on _____ and SNAP and syntaxin SNAREs are found on ______

A

vesicles

target membranes

68
Q

Notice that _______ determine specificity of docking location with the SNAREs on the outside of the vesicle.

A

GTP-binding proteins (Rab proteins)

69
Q

These GTP-BPs can also regulate ______

A

coat assembly (all kinds).

70
Q

Once a vesicle’s budded off from the ER, it’s moved to the _____ via the ______.
What are the motor proteins that move them?

A

Golgi via the cytoskeletal network

The motor proteins that move them are dynein and kinesin.

71
Q

There’s a “vesicular-tubular cluster” that functions to ____

A

pre-packages the proteins before they get to the Golgi.

72
Q

Exocytic pathway:

A

getting proteins to the organelles they’re going to.

73
Q

Endocytic pathway:

A

getting proteins, within their target organelles, to their sites of action.

74
Q

Notice that the interiors of lymphocytes are almost entirely made up of what?

A

ER, like most cells that produce

massive amount of proteins (in this case antibodies).

75
Q

GPI-linked proteins will eventually end up where?

A

on the outside of the cell’s plasma membrane.

76
Q

Glycosyl-phosphatidyl-inositol link (GPI) links the

A

protein to the cell membrane

77
Q

KDEL protein function?

A

protein for retrieving improperly transported packages.

M2M Exam 3 wk 2 (11 decks)

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