The cytoskeleton Flashcards by Micro Bio

Why do eukaryotic cells need a cytoskeleton?

large
cannot rely on diffusion
need motors & tracks

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Quick facts about Actin filaments?

7nm
polymer of actin
tracks for myosin

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Quick facts about Microtubules?

25nm
polymer of alpha-beta tubulin dimers
tracks for kinesin and dyenin

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Quick facts about Intermediate filaments?

10nm
polymers of intermediate filament proteins
no associated motors

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How do Microtubules help a cell develop polarity?

minus end in centrosome

- plus end towards plasma membrane

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What is the structure of Microtubules?

alpha-beta tubulin dimers = 8nm
b-tubulin ‘plus’
a-tubulin ‘minus’
13 protofilaments

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Which ends of the microtubules are fast/slow growing?

'plus' = fast
'minus' = slow

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What is involved in the MTOC?

microtubules grow out of MTOC
centrioles
pericentriolar matrix

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What is involved in the polymerisation and depolymerisation of microtubules?

GTP-tubulin subunits add to ‘plus’

if stops - GDP capped tubulin - peeling behaviour

GTP-tubulin CAP lost = depolymerise - catastrophe

only b-tubulin hydrolyses GTP - exposed at ‘plus’

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How can microtubules be post-translationally modified?

C-terminal tail = polyglutamated/glycalated

C-terminal tyrosine removed

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3 roles of microtubules?

1) trafficking of cargo
2) mitosis
3) Cilium

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How does the motor protein Kinesin use Microtubules as tracks?

traffics to ‘plus’
takes 8nm steps
ATP hydrolysis powered
40 diff. types

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What is the structure of kinesin motor protein?

Dimer
2 motor domins
tail can bind to light chains

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How are kinesins important in mitosis?

trafficking of EG5
EG5 tetramer binds between microtubules
builds spindle

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How does the motor protein Dynein use microtubules as tracks?

traffics to ‘minus’

- cytoplasmic dynein 1 & 2

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What is the structure of Dynein motor protein?

triple A ring made of 6 triple A motifs
linker
found in cilia & cytoplasm

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What is the Dynein power stroke?

linker goes across top and hits across AAA2-4

steric clash when linker is hit

linker moves out way forming bent conformation = pre-power stroke conformation

What are MAPS?

microtubule associated proteins

Whats is TAU protein?

disease protein
mainly in axons
stabilises microtubules

small amount in DNA suggesting nuclear function

How is binding of TAU to microtubules regulated?

by phosphorylation

TAU affinity for MTs decreases when hyper-phosphorylated

What is Spastin?

disease protein

severs stable regions of microtubules

ataches to C-terminal tubulin ‘tails’ - dislodges tubulin from MT lattic

How is severing by Spastin stimulated?

polyglutamationf of C-terminal tubulin tail by TTLL6

How are microtubules involved in mitosis?

form scaffold for sorting chromosomes

form spindle

dynein & kinesins involved

How are microtubules involved in Cilia?

motile or immotile

motile have pair of central microtubules

‘9+2’ - 2 central microtubule surrounded by 9 MT doublets

How are Kinesin and Dynein-2 involved in cilia?

traffic intra-flagellar (IFT) cargoes build/maintain all cilia

What are diseases associated with microtubules?

TUBA1A - polymcirogyria - small gyri TUBB2B - Diffuse pachygyria - smooth brain

How do neurons migrate in the developing brain?

neural progenitors in ventricular zone migrate to cortical plate migration in cerebral cortex & hippocampus

What do mutations in TUBA1A cause?

affect binding of kinesins affect polymerisation microlissencephaly lissencephaly pachygyriA polymicrogyria

What happens in Lissencephaly?

- smooth brain - small head - mental retardation

What are 2 common mutations in TUBA1A?

- R402H - R264C affect binding of proteins to MTs reduced traficking reduced microtubule stability

What do mutations in kinesins cause?

hereditary spastic paraplegia

What happens in hereditary spastic paraplegia?

- Kif5a - 56 missense - in motor domain - spasticity in legs - kinesin movement affected - problems at synapses

What are the mutations in Kif5a that causes SPG?

reduce velocity - N256S, K253N reducing binding - R280S, K253N

What diseases is TAU protein involved in?

Alzheimers Progressive supranuclear palsy Cortico-basal degeneration dementia parksinsonism

What are the mutations in TAU protein?

- in microtubule binding domain - reduced affinity for microtubules - aggregation missense & splicing mutatons

How does TAU cause disease

detach from microtubules microtubule disassembly reduced trafficking misolocalisation to presynapse synaptic dysfunction

What is the synaptic dysfunction of Tau?

Tau recruits enzyme TTLL6 polyglutamates tubulin Tau unbinds Spastin recruited severs & destabilises

What is taxol?

microtubule stabilising drug cancer treatment induces mitotic arrest cell death results from chromosome mis-segregation on multipolar spindles

What is involved in ciliopathies?

kinesin and dynein lots of syndromes

What does mutation in dynein heavy chain cause?

PCD - primary cilia dyskinesia altered bending of distal region ability of dynein heavy chain to generate movement