Cytoskeleton: Microtubules Flashcards

1
Q

What are the 3 cytosolic proteins that make the cytoskeleton?

A

Microfilaments, actin filaments, intermediate filaments

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2
Q

Microtubule and actin can do what rapidly?

A

Grow and shrink

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3
Q

Where do microtubules originate?

A

Centrosome

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4
Q

What is the smallest filament of cytoskeleton?

A

actin

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5
Q

What are the main functions of the cytoskeleton?

A
Support & strength
cell movement
intracellular movement
cytokenesis AKA mitosis
changes in cell shape
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6
Q

Name two microtubule motor proteins we have to know

A

dynein & kinesin

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7
Q

What is the name of the motor protein on actin?

A

myosin

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8
Q

Axons are full of _____ to allow transport of vesicles

A

microtubules

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9
Q

What protein subunits make up a microtubule?

A

alpha-tubulin and beta-tubuiln

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10
Q

How many columns of tubulin molecules make up a microtubule?

A

13

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11
Q

Where do microtubules originate from in the cell?

A

centrosome

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12
Q

Which filament is the most rigid and provide the “support beams”

A

microtubules

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13
Q

What acts as the motile elements in cilia & flagella?

A

microtubules

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14
Q

Where is the location of actin in a cell?

A

Around the perimeter

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15
Q

What is the diameter of microtubule?

A

25 nm

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16
Q

What is a protofilament?

A

A linear arrangement of 13 alpha and beta tubulin

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17
Q

Describe the structure of a microtubule

A

straight and hollow tubes, made up of a protofilaments

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18
Q

How does the microtubule shrink and grow?

A

alpha and beta dimers polymerize end to end

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19
Q

What is the charge of the alpha and beta subunits of microtubules?

A

alpha -

beta +

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20
Q

Describe the charge of a microtubule

A

It grows alpha then beta subunits, so beta is positive end and its farthest from cell nucleus, towards periphery of cell. the negative end is at the centrosome, by the nucleus

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21
Q

What is needed in order for beta dimers to bind together?

A

GTP

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22
Q

What part of microtubule is capped with GTP?

A

beta-tubulin

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23
Q

Describe the difference b/w a GDP and GTP bound alpha/beta dimer in a microtubule

A

If it is GDP bound it is unstable, it will depolymerize. If it is GTP bound it is stable and will keep growing/associating with each other.

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24
Q

There are GDP bound dimers at negative end of microtubule, what stops them from breaking apart?

A

There are a bunch of other GTP bound dimers on top that keep it together

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25
Q

Where does depolymerization occur of microtubule

A

Top of microtuble (positive end)

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26
Q

Why is the bottom part of a microtubule bound to GDP?

A

GTP will gradually be hydrolysed to GDP and phosphate

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27
Q

What happens if GDP-tubulin reach growing end?

A

Catastrophe - depolymerization. Loss of that microtubule

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28
Q

What is catastrophe?

A

When the GDP-tubulin catches up to growing end and then depolymerisation

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29
Q

When GTP-tubulin allows for more growth on + side of microtubule, what is it called?

A

Rescue

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30
Q

Explain the dynamic instability of microtubules

A

constant catastrophe and rescue. The microtubule is either growing or shrinking. GTP hydrolysis is either caught up or enough GTP is added so that the microtubule can grow

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31
Q

What is the growth rate of a microtubule proportionate to?

A

concentration of GTP-tubulin dimers

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32
Q

What does beta tubulin hydrolyse?

A

GTP to GDP

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33
Q

What happens if hydrolysis of GTP catches up with dimer addition?

A

catastrophe - microtubule will shrink

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34
Q

What is a microtubule singlet?

A

13 protofilaments - a single column of actin and beta tubulin

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35
Q

What is the purpose of a microtubule singlet?

A

carry & move vesicles, organelles, chromosomes

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36
Q

What is a microtubule doublet?

A

Two rings of actin and beta tubulin

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37
Q

Where is a doublet microtubule found?

A

cilia & flagella

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38
Q

What is an axoneme?

A

the central strand of a cilium or flagellum

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39
Q

What is an axoneme made up of?

A

Doublet microtubule

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40
Q

What does MTOC stand for?

A

Microtubule organizing center

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41
Q

What makes up a centrosome?

A

2 centrioles

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42
Q

What makes up a centriole?

A

9 triplet microtubules

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43
Q

What is the purpose of MTOC?

A

Where microtubules originate from and radiate out from

44
Q

What will happen to centrosome during mitosis?

A

It will be duplicated

45
Q

Where is negative end of microtubule?

A

Anchored in MTOC

46
Q

Where is positive end of microtubule?

A

at periphery of cell

47
Q

Kinesin and Dynein are both examples of

A

motor proteins

48
Q

What is the function of kinesin?

A

carries material towards + end of microtubule

49
Q

What is the function of Dynein?

A

Carries material toward - end of microtubule

50
Q

What is anterograde

A

toward positive end of microtubule

51
Q

What is retrograde

A

Toward negative end of microtubule

52
Q

What is a basal body?

A

MTOC for axoneme

53
Q

What is the function of gamma tubulin in microtubule?

A

It is the scaffold for growth in MTOC. It forms a ring outside of centrosome for which microtubule singlets can grow from

54
Q

Describe how two centrioles make a centrosome

A

The two centrioles join at right angles to each other

55
Q

What is a centriole comprised of?

A

9 triplet MTs

56
Q

Explain microtubules in dendrites

A

The positive and negative end can be in either direction, it’s not understood why

57
Q

What forms the spindle poles in mitosis?

A

MTOCs

58
Q

What do motor proteins need to move along microtubule?

A

ATP

59
Q

Describe the structure of motor protein

A

Cargo (bound to the protein) - tail - two motor heads with ATPase activity

60
Q

How do motor proteins carry vesicles along microtubule

A

They “walk.” They have two motor heads that bind to ATP and “walk” along microtubule

61
Q

Which motor protein is Anterograde?

A

kinesin

62
Q

Which motor protein is retrograde?

A

Dynein

63
Q

How do nerve cells transmit their signals?

A

via microtubules with kinesin or dynein

64
Q

How do we know which way a vesicle will move along a microtubule?

A

It is bound to both kinesin & dynein. It goes the direction of whatever is bound to it more

65
Q

What is the function of MAPs with microtubules? What is the ultimate result?

A

They stabilize microtubule. They can bind microtubule to other cell structures. When they are bound the microtubule is longer and less dynamic.

66
Q

What is the function of catastrophe factor? What is the ultimate result?

A

It binds to GTP and breaks it apart → destabilizes microtubule. Results in shorter and more dynamic microtbules

67
Q

Describe the domains of MAP

A

2 domains. One is bound to tubulin, the other can also be bound to tubulin or to another cellular structure

68
Q

What is the tau protein?

A

MAP!

69
Q

Key words: hyperphosphorylated tau, neurofibrillated tangles, B-amyloid, senile, presenile, apoE4, early/late onset is what disease?

A

Alzheimer’s Disease

70
Q

Characteristic: dementia is what disease?

A

Alzheimer’s Disease

71
Q

What is the mechanism for alzheimer’s disease?

A

Hyperphosphorylated tau (MAP) ! forms NFTs ! decrease function of microtubules (depolymerization & disruption of axon transport); Accumulation of Bamyloid/senile plaques due to accumulation of B-amyloid peptides ! progressive neuronal damage

72
Q

What is the mode of inheritance for alzheimer’s disease?

A

AD or multifactoral

73
Q

Where is the defect located in Alzheimer’s Disease?

A

tau (MAP) & B-amyloid/senile plaques

74
Q

hyperphosphorylated tau is a cause of what disease?

A

Alzheimer’s Disease

75
Q

What does NFT stand for?

A

Neurofibrillary tangles

76
Q

What causes formation of NFTs?

A

hyperphosphorylation of Tau

77
Q

Where do NFTs accumulate?

A

In beta A plaques

78
Q

Why are NFTs bad?

A

They disrupt axon transport b/c of microtubule depolymerization

79
Q

Where do beta amyloid plaques accumulate?

A

Outside of cells

80
Q

What is another name for beta amyloid plaque?

A

senile plaques

81
Q

How are beta amyloid plaques made?

A

beta amyloid peptide, a peptide that is normally released by cells into extracellular space, is released but is too long. Because they are too big they clump together and form plaque

82
Q

What is the function of secretase in alzheimer’s disease?

A

Secretase cleaves transmembrane protein to release beta amyloid peptide. In alzheimer’s the secretase abnormally processes the transmembrane protein and the peptide is too big.

83
Q

Secretases are encoded by what genes?

A

Presinilin

84
Q

What genes are involved in AD alzheimers?

A

Presinilin 1 & 2

beta amyloid precurser

85
Q

Why do pts with down syndrome eventually develop alzheimers?

A

The gene for beta amyloid precurser is on chromosome 21 - down syndrome pts will have three of these genes, more likely to get alzheimers.

86
Q

Early onset alzheimers mean symptoms show before what age?

A

60

87
Q

Progressive degeneration of cerebral cortex is the definition of:

A

dementia

88
Q

What gene increases the risk for developing late onset alzheimers?

A

Apolipoprotein E

89
Q

What is another name for apolipopprotein E?

A

ε4 allele

90
Q

If somebody is heterozygous for ε4 allele, what does that mean?

A

More likely than rest of pop. to develop alzheimers. 3x more likely than rest of pop.

91
Q

If somebody is homozygous for ε4 allele what does that mean?

A

15x more likely than rest of pop. to develop alzheimers

92
Q

Multifactoral alzheimer is late or early onset?

A

late

93
Q

The Apo E2 gene means what for alzheiemrs?

A

reduced risk

94
Q

What are the phases in cell cylcle?

A

G1 S G2 M

95
Q

What happens in G phases?

A

cell growth

96
Q

How many classes of microtubules are there?

A

3

97
Q

What are the 3 kinds of microtubules involved in mitotic spindle

A

Astral microtubules, kinetochore microtubules, polar microtubles

98
Q

Where do the astral, kinetochore, and polar microtubules radiate from?

A

centrosome

99
Q

Which microtubule attaches to the kinetochore on chromatids?

A

inetochore microtubule

100
Q

What motor protein is associated with sister chromatids? What is the function?

A

Dynein - they walk the sister chromatids toward the nearest spindle pole

101
Q

What is the function of kinetochore microtubules?

A

pull sister chromatids apart in cell division

102
Q

What motor protein is associated with kinetochore chromatids?

A

Dynein

103
Q

What is the function of polar microtubules?

A

Pushing the two spindles apart, preparing cell for division. More separation of chromatids.

104
Q

When do centrioles replicate?

A

In S phase - before mitosis

105
Q

What is the function of the astral microtubules?

A

Attaches to cell wall - holds everything in place

106
Q

What kind of motor protein is associated with polar microtubules?

A

Kinesin

107
Q

What is the smallest subunit making up a microtubule?

A

tubulin dimer