Cytoskeleton: Microtubules Flashcards
1
Q
What are the 3 cytosolic proteins that make the cytoskeleton?
A
Microfilaments, actin filaments, intermediate filaments
2
Q
Microtubule and actin can do what rapidly?
A
Grow and shrink
3
Q
Where do microtubules originate?
A
Centrosome
4
Q
What is the smallest filament of cytoskeleton?
A
actin
5
Q
What are the main functions of the cytoskeleton?
A
Support & strength cell movement intracellular movement cytokenesis AKA mitosis changes in cell shape
6
Q
Name two microtubule motor proteins we have to know
A
dynein & kinesin
7
Q
What is the name of the motor protein on actin?
A
myosin
8
Q
Axons are full of _____ to allow transport of vesicles
A
microtubules
9
Q
What protein subunits make up a microtubule?
A
alpha-tubulin and beta-tubuiln
10
Q
How many columns of tubulin molecules make up a microtubule?
A
13
11
Q
Where do microtubules originate from in the cell?
A
centrosome
12
Q
Which filament is the most rigid and provide the “support beams”
A
microtubules
13
Q
What acts as the motile elements in cilia & flagella?
A
microtubules
14
Q
Where is the location of actin in a cell?
A
Around the perimeter
15
Q
What is the diameter of microtubule?
A
25 nm
16
Q
What is a protofilament?
A
A linear arrangement of 13 alpha and beta tubulin
17
Q
Describe the structure of a microtubule
A
straight and hollow tubes, made up of a protofilaments
18
Q
How does the microtubule shrink and grow?
A
alpha and beta dimers polymerize end to end
19
Q
What is the charge of the alpha and beta subunits of microtubules?
A
alpha -
beta +
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
21
Q
What is needed in order for beta dimers to bind together?
A
GTP
22
Q
What part of microtubule is capped with GTP?
A
beta-tubulin
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.
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
25
Where does depolymerization occur of microtubule
Top of microtuble (positive end)
26
Why is the bottom part of a microtubule bound to GDP?
GTP will gradually be hydrolysed to GDP and phosphate
27
What happens if GDP-tubulin reach growing end?
Catastrophe - depolymerization. Loss of that microtubule
28
What is catastrophe?
When the GDP-tubulin catches up to growing end and then depolymerisation
29
When GTP-tubulin allows for more growth on + side of microtubule, what is it called?
Rescue
30
Explain the dynamic instability of microtubules
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
31
What is the growth rate of a microtubule proportionate to?
concentration of GTP-tubulin dimers
32
What does beta tubulin hydrolyse?
GTP to GDP
33
What happens if hydrolysis of GTP catches up with dimer addition?
catastrophe - microtubule will shrink
34
What is a microtubule singlet?
13 protofilaments - a single column of actin and beta tubulin
35
What is the purpose of a microtubule singlet?
carry & move vesicles, organelles, chromosomes
36
What is a microtubule doublet?
Two rings of actin and beta tubulin
37
Where is a doublet microtubule found?
cilia & flagella
38
What is an axoneme?
the central strand of a cilium or flagellum
39
What is an axoneme made up of?
Doublet microtubule
40
What does MTOC stand for?
Microtubule organizing center
41
What makes up a centrosome?
2 centrioles
42
What makes up a centriole?
9 triplet microtubules
43
What is the purpose of MTOC?
Where microtubules originate from and radiate out from
44
What will happen to centrosome during mitosis?
It will be duplicated
45
Where is negative end of microtubule?
Anchored in MTOC
46
Where is positive end of microtubule?
at periphery of cell
47
Kinesin and Dynein are both examples of
motor proteins
48
What is the function of kinesin?
carries material towards + end of microtubule
49
What is the function of Dynein?
Carries material toward - end of microtubule
50
What is anterograde
toward positive end of microtubule
51
What is retrograde
Toward negative end of microtubule
52
What is a basal body?
MTOC for axoneme
53
What is the function of gamma tubulin in microtubule?
It is the scaffold for growth in MTOC. It forms a ring outside of centrosome for which microtubule singlets can grow from
54
Describe how two centrioles make a centrosome
The two centrioles join at right angles to each other
55
What is a centriole comprised of?
9 triplet MTs
56
Explain microtubules in dendrites
The positive and negative end can be in either direction, it's not understood why
57
What forms the spindle poles in mitosis?
MTOCs
58
What do motor proteins need to move along microtubule?
ATP
59
Describe the structure of motor protein
Cargo (bound to the protein) - tail - two motor heads with ATPase activity
60
How do motor proteins carry vesicles along microtubule
They "walk." They have two motor heads that bind to ATP and "walk" along microtubule
61
Which motor protein is Anterograde?
kinesin
62
Which motor protein is retrograde?
Dynein
63
How do nerve cells transmit their signals?
via microtubules with kinesin or dynein
64
How do we know which way a vesicle will move along a microtubule?
It is bound to both kinesin & dynein. It goes the direction of whatever is bound to it more
65
What is the function of MAPs with microtubules? What is the ultimate result?
They stabilize microtubule. They can bind microtubule to other cell structures. When they are bound the microtubule is longer and less dynamic.
66
What is the function of catastrophe factor? What is the ultimate result?
It binds to GTP and breaks it apart → destabilizes microtubule. Results in shorter and more dynamic microtbules
67
Describe the domains of MAP
2 domains. One is bound to tubulin, the other can also be bound to tubulin or to another cellular structure
68
What is the tau protein?
MAP!
69
Key words: hyperphosphorylated tau, neurofibrillated tangles, B-amyloid, senile, presenile, apoE4, early/late onset is what disease?
Alzheimer's Disease
70
Characteristic: dementia is what disease?
Alzheimer's Disease
71
What is the mechanism for alzheimer's disease?
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
What is the mode of inheritance for alzheimer's disease?
AD or multifactoral
73
Where is the defect located in Alzheimer's Disease?
tau (MAP) & B-amyloid/senile plaques
74
hyperphosphorylated tau is a cause of what disease?
Alzheimer's Disease
75
What does NFT stand for?
Neurofibrillary tangles
76
What causes formation of NFTs?
hyperphosphorylation of Tau
77
Where do NFTs accumulate?
In beta A plaques
78
Why are NFTs bad?
They disrupt axon transport b/c of microtubule depolymerization
79
Where do beta amyloid plaques accumulate?
Outside of cells
80
What is another name for beta amyloid plaque?
senile plaques
81
How are beta amyloid plaques made?
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
What is the function of secretase in alzheimer's disease?
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
Secretases are encoded by what genes?
Presinilin
84
What genes are involved in AD alzheimers?
Presinilin 1 & 2
| beta amyloid precurser
85
Why do pts with down syndrome eventually develop alzheimers?
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
Early onset alzheimers mean symptoms show before what age?
60
87
Progressive degeneration of cerebral cortex is the definition of:
dementia
88
What gene increases the risk for developing late onset alzheimers?
Apolipoprotein E
89
What is another name for apolipopprotein E?
ε4 allele
90
If somebody is heterozygous for ε4 allele, what does that mean?
More likely than rest of pop. to develop alzheimers. 3x more likely than rest of pop.
91
If somebody is homozygous for ε4 allele what does that mean?
15x more likely than rest of pop. to develop alzheimers
92
Multifactoral alzheimer is late or early onset?
late
93
The Apo E2 gene means what for alzheiemrs?
reduced risk
94
What are the phases in cell cylcle?
G1 S G2 M
95
What happens in G phases?
cell growth
96
How many classes of microtubules are there?
3
97
What are the 3 kinds of microtubules involved in mitotic spindle
Astral microtubules, kinetochore microtubules, polar microtubles
98
Where do the astral, kinetochore, and polar microtubules radiate from?
centrosome
99
Which microtubule attaches to the kinetochore on chromatids?
inetochore microtubule
100
What motor protein is associated with sister chromatids? What is the function?
Dynein - they walk the sister chromatids toward the nearest spindle pole
101
What is the function of kinetochore microtubules?
pull sister chromatids apart in cell division
102
What motor protein is associated with kinetochore chromatids?
Dynein
103
What is the function of polar microtubules?
Pushing the two spindles apart, preparing cell for division. More separation of chromatids.
104
When do centrioles replicate?
In S phase - before mitosis
105
What is the function of the astral microtubules?
Attaches to cell wall - holds everything in place
106
What kind of motor protein is associated with polar microtubules?
Kinesin
107
What is the smallest subunit making up a microtubule?
tubulin dimer
