Lecture 10 and 11 Flashcards

1
Q

What does vesicle trafficking mediate?

A

Constant flow of proteins throughout the cell

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2
Q

What goes through the retrieval pathway?

A

Retrograde trafficking
- Golgi –> ER
- Late endosome –> Golgi
- Early endosome –> Golgi
- Secretory vesicles –> Golgi
- Early endosome –> Cell exterior

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3
Q

What goes through the endocytic pathway?

A
  • Cell Exterior –> Early Endosome
  • Early Endosome –> Late Endosome
  • Late Endosome –> Lysosome
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4
Q

What goes through the biosynthetic/secretory pathway?

A
  • ER –> Golgi
  • Golgi –> Late Endosome
  • Golgi –> Early Endosome
  • Golgi –> Cell Exterior
  • Golgi –> Secretory Vesicles
  • Late Endosome –> Lysosome
  • Secretory Vesicles –> Cell Exterior
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5
Q

What does the golgi apparatus/complex consist of?

A

Specific orientation of flattened stacked membrane compartments (cisternae; 4 to 6 cisternae per stack) that “mature” over time

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6
Q

What is the golgi apparatus/complex divided into?

A
  • Cis-face: Entry face at beginning of golgi (near ER)
  • Medial: Sandwiched by cis and trans cisternae
  • Trans-face: Exit face just prior to leaving golgi
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7
Q

How do proteins enter the golgi apparatus/complex?

A

Through the cis golgi network (CGN)

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8
Q

How do proteins exit the golgi apparatus/complex?

A

Through the trans golgi network (TGN)

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9
Q

Where are proteins post-translationally modified in the golgi?

A

In various sub-compartments

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10
Q

What are the two models for golgi maturation?

A

Vesicle transport and cisternal maturation

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11
Q

What is involved in the vesicle transport model?

A
  • Golgi is static and enzymes remain in each location
  • Vesicles fuse and leave the structures in sequence
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12
Q

What is involved in the cisternal maturation model?

A
  • Golgi structure is dynamic and entire cisternae move
  • Cis-cisternae eventually become mid-cisternae and then trans-cisternae
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13
Q

Why do we need retrograde flow back into cis-cisternae?

A

Because processing enzymes have to make their way back to where they started

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14
Q

What are coat proteins?

A

Proteins which “coat” or cover the vesicle

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15
Q

What types of coat proteins are there?

A
  • Clathrin
  • Coat protein I (COPI)
  • Coat protein II (COPII)
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16
Q

What does the presence of a particular coat protein depend on?

A

Where the vesicles originate from

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17
Q

Where does clathrin originate from?

A

Transport vesicles from plasma membrane and between endosomal and golgi compartments

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18
Q

Where does COP I originate from?

A

Bud off from Golgi

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19
Q

Where does COP II originate from?

A

Early transport vesicles from ER

20
Q

What is each clathrin subunit composed of?

A

Three large (heavy) chains and three small (light) chains that form triskelion

21
Q

What do triskelions form?

A

Combinations of hexagons and pentagons (polyhedral cages)

22
Q

What is clathrin attached to?

A

Adaptor molecules in the cell membrane

23
Q

When does the clathrin coat form from the triskelion structure?

A

Upon endocytosis

24
Q

When is the clathrin coat shed?

A

Prior to vesicle fusion and transport

25
Q

What do adaptor proteins form?

A

A second coat around vesicles

26
Q

What does the adaptor protein coat do?

A

Serves to anchor cargo receptors into the vesicle

27
Q

What does each type of adaptor recognize?

A

Different receptors

28
Q

What are the key regulatory molecules of vesicle trafficking?

A

Phosphatidyl inositol phosphatases (PIPs)

29
Q

What do different PIs bind?

A

Different proteins

30
Q

Where do distinct sets of phosphatases and kinases reside in?

A

Different vesicle populations

31
Q

Why do distinct sets of phosphatases and kinases reside in different vesicle populations?

A

To alter PI molecules

32
Q

What does the presence of different phosphoinositide molecules at certain membrane regions do?

A

Regulate protein binding in those regions

33
Q

What is required for vesicle fusion?

A

Energy

34
Q

What is required to assist in membrane fusion?

A

Dynamin

35
Q

What domains does dynamin have?

A

PIP2 binding domain and GTPase domain

36
Q

What diseases are caused by dynamin mutations?

A
  • Charcot Marie Tooth (CMT) disease
  • Centronuclear myopathy (CNM) disease
  • Some forms of epilepsy
37
Q

What is Charcot Marie Tooth (CMT) disease?

A

A progressive nerve disease
- Named after the 3 doctors who discovered it in 1886
- 1 in 2,500 births
- Leads to loss of myelin sheath and peripheral nerve damage

38
Q

What does centronuclear myopathy (CNM) disease cause?

A

Muscle weakness that can range from mild to severe (dynamin 2 gene)

39
Q

What are COPI and COPII vesicles?

A

Other regulatory molecules that control vesicle formation and recruit coat proteins to specific membrane regions

40
Q

What do coat recruitment GTPases do?

A

Control when and where clathrin and COP coated vesicles are formed

41
Q

What are Arfs?

A

ADP ribosylation factors
- GTPase which is myristoylated at the N-terminus (anchors to membrane)
- Responsible for clathrin and COPI vesicle formation

42
Q

What is Sar1?

A

Secretion-associated and Ras-related
- When bound to GTP, Sar1 can bind to cytoplasmic face of membrane
- When in membrane, it recruits COPII coat proteins (Secs)

43
Q

What forms the inner COPII coat?

A

Sec23/24

44
Q

What forms the outer COPII coat?

A

Sec 13/31

45
Q

What do mature COPII vesicles contain?

A

Sar1, Sec 23/24, and Sec 13/31
- Dynamin does not appear to be required for scission of the vesicle for COP coated vesicles

46
Q

When do COPII proteins dissociate?

A

Upon release of the vesicle