Cytoskeleton: Microtubules Flashcards
What are the 3 cytosolic proteins that make the cytoskeleton?
Microfilaments, actin filaments, intermediate filaments
Microtubule and actin can do what rapidly?
Grow and shrink
Where do microtubules originate?
Centrosome
What is the smallest filament of cytoskeleton?
actin
What are the main functions of the cytoskeleton?
Support & strength cell movement intracellular movement cytokenesis AKA mitosis changes in cell shape
Name two microtubule motor proteins we have to know
dynein & kinesin
What is the name of the motor protein on actin?
myosin
Axons are full of _____ to allow transport of vesicles
microtubules
What protein subunits make up a microtubule?
alpha-tubulin and beta-tubuiln
How many columns of tubulin molecules make up a microtubule?
13
Where do microtubules originate from in the cell?
centrosome
Which filament is the most rigid and provide the “support beams”
microtubules
What acts as the motile elements in cilia & flagella?
microtubules
Where is the location of actin in a cell?
Around the perimeter
What is the diameter of microtubule?
25 nm
What is a protofilament?
A linear arrangement of 13 alpha and beta tubulin
Describe the structure of a microtubule
straight and hollow tubes, made up of a protofilaments
How does the microtubule shrink and grow?
alpha and beta dimers polymerize end to end
What is the charge of the alpha and beta subunits of microtubules?
alpha -
beta +
Describe the charge of a microtubule
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
What is needed in order for beta dimers to bind together?
GTP
What part of microtubule is capped with GTP?
beta-tubulin
Describe the difference b/w a GDP and GTP bound alpha/beta dimer in a microtubule
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.
There are GDP bound dimers at negative end of microtubule, what stops them from breaking apart?
There are a bunch of other GTP bound dimers on top that keep it together
Where does depolymerization occur of microtubule
Top of microtuble (positive end)
Why is the bottom part of a microtubule bound to GDP?
GTP will gradually be hydrolysed to GDP and phosphate
What happens if GDP-tubulin reach growing end?
Catastrophe - depolymerization. Loss of that microtubule
What is catastrophe?
When the GDP-tubulin catches up to growing end and then depolymerisation
When GTP-tubulin allows for more growth on + side of microtubule, what is it called?
Rescue
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
What is the growth rate of a microtubule proportionate to?
concentration of GTP-tubulin dimers
What does beta tubulin hydrolyse?
GTP to GDP
What happens if hydrolysis of GTP catches up with dimer addition?
catastrophe - microtubule will shrink
What is a microtubule singlet?
13 protofilaments - a single column of actin and beta tubulin
What is the purpose of a microtubule singlet?
carry & move vesicles, organelles, chromosomes
What is a microtubule doublet?
Two rings of actin and beta tubulin
Where is a doublet microtubule found?
cilia & flagella
What is an axoneme?
the central strand of a cilium or flagellum
What is an axoneme made up of?
Doublet microtubule
What does MTOC stand for?
Microtubule organizing center
What makes up a centrosome?
2 centrioles
What makes up a centriole?
9 triplet microtubules
What is the purpose of MTOC?
Where microtubules originate from and radiate out from
What will happen to centrosome during mitosis?
It will be duplicated
Where is negative end of microtubule?
Anchored in MTOC
Where is positive end of microtubule?
at periphery of cell
Kinesin and Dynein are both examples of
motor proteins
What is the function of kinesin?
carries material towards + end of microtubule
What is the function of Dynein?
Carries material toward - end of microtubule
What is anterograde
toward positive end of microtubule
What is retrograde
Toward negative end of microtubule
What is a basal body?
MTOC for axoneme
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
Describe how two centrioles make a centrosome
The two centrioles join at right angles to each other
What is a centriole comprised of?
9 triplet MTs
Explain microtubules in dendrites
The positive and negative end can be in either direction, it’s not understood why
What forms the spindle poles in mitosis?
MTOCs
What do motor proteins need to move along microtubule?
ATP
Describe the structure of motor protein
Cargo (bound to the protein) - tail - two motor heads with ATPase activity
How do motor proteins carry vesicles along microtubule
They “walk.” They have two motor heads that bind to ATP and “walk” along microtubule
Which motor protein is Anterograde?
kinesin
Which motor protein is retrograde?
Dynein
How do nerve cells transmit their signals?
via microtubules with kinesin or dynein
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
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.
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
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
What is the tau protein?
MAP!
Key words: hyperphosphorylated tau, neurofibrillated tangles, B-amyloid, senile, presenile, apoE4, early/late onset is what disease?
Alzheimer’s Disease
Characteristic: dementia is what disease?
Alzheimer’s Disease
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
What is the mode of inheritance for alzheimer’s disease?
AD or multifactoral
Where is the defect located in Alzheimer’s Disease?
tau (MAP) & B-amyloid/senile plaques
hyperphosphorylated tau is a cause of what disease?
Alzheimer’s Disease
What does NFT stand for?
Neurofibrillary tangles
What causes formation of NFTs?
hyperphosphorylation of Tau
Where do NFTs accumulate?
In beta A plaques
Why are NFTs bad?
They disrupt axon transport b/c of microtubule depolymerization
Where do beta amyloid plaques accumulate?
Outside of cells
What is another name for beta amyloid plaque?
senile plaques
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
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.
Secretases are encoded by what genes?
Presinilin
What genes are involved in AD alzheimers?
Presinilin 1 & 2
beta amyloid precurser
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.
Early onset alzheimers mean symptoms show before what age?
60
Progressive degeneration of cerebral cortex is the definition of:
dementia
What gene increases the risk for developing late onset alzheimers?
Apolipoprotein E
What is another name for apolipopprotein E?
ε4 allele
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.
If somebody is homozygous for ε4 allele what does that mean?
15x more likely than rest of pop. to develop alzheimers
Multifactoral alzheimer is late or early onset?
late
The Apo E2 gene means what for alzheiemrs?
reduced risk
What are the phases in cell cylcle?
G1 S G2 M
What happens in G phases?
cell growth
How many classes of microtubules are there?
3
What are the 3 kinds of microtubules involved in mitotic spindle
Astral microtubules, kinetochore microtubules, polar microtubles
Where do the astral, kinetochore, and polar microtubules radiate from?
centrosome
Which microtubule attaches to the kinetochore on chromatids?
inetochore microtubule
What motor protein is associated with sister chromatids? What is the function?
Dynein - they walk the sister chromatids toward the nearest spindle pole
What is the function of kinetochore microtubules?
pull sister chromatids apart in cell division
What motor protein is associated with kinetochore chromatids?
Dynein
What is the function of polar microtubules?
Pushing the two spindles apart, preparing cell for division. More separation of chromatids.
When do centrioles replicate?
In S phase - before mitosis
What is the function of the astral microtubules?
Attaches to cell wall - holds everything in place
What kind of motor protein is associated with polar microtubules?
Kinesin
What is the smallest subunit making up a microtubule?
tubulin dimer