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MICR2120 Cell Biology & Disease > The cytoskeleton > Flashcards

The cytoskeleton Flashcards

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1
Q

Why do eukaryotic cells need a cytoskeleton?

A
  • large
  • cannot rely on diffusion
  • need motors & tracks
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2
Q

Quick facts about Actin filaments?

A
  • 7nm
  • polymer of actin
  • tracks for myosin
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3
Q

Quick facts about Microtubules?

A
  • 25nm
  • polymer of alpha-beta tubulin dimers
  • tracks for kinesin and dyenin
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4
Q

Quick facts about Intermediate filaments?

A
  • 10nm
  • polymers of intermediate filament proteins
  • no associated motors
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5
Q

How do Microtubules help a cell develop polarity?

A
  • minus end in centrosome

- plus end towards plasma membrane

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6
Q

What is the structure of Microtubules?

A
  • alpha-beta tubulin dimers = 8nm
  • b-tubulin ‘plus’
  • a-tubulin ‘minus’
  • 13 protofilaments
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7
Q

Which ends of the microtubules are fast/slow growing?

A 
'plus' = fast
'minus' = slow
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8
Q

What is involved in the MTOC?

A
  • microtubules grow out of MTOC
  • centrioles
  • pericentriolar matrix
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9
Q

What is involved in the polymerisation and depolymerisation of microtubules?

A

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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10
Q

How can microtubules be post-translationally modified?

A

C-terminal tail = polyglutamated/glycalated

C-terminal tyrosine removed

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11
Q

3 roles of microtubules?

A

1) trafficking of cargo
2) mitosis
3) Cilium

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12
Q

How does the motor protein Kinesin use Microtubules as tracks?

A

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

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13
Q

What is the structure of kinesin motor protein?

A

Dimer
2 motor domins
tail can bind to light chains

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14
Q

How are kinesins important in mitosis?

A

trafficking of EG5
EG5 tetramer binds between microtubules
builds spindle

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15
Q

How does the motor protein Dynein use microtubules as tracks?

A
  • traffics to ‘minus’

- cytoplasmic dynein 1 & 2

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16
Q

What is the structure of Dynein motor protein?

A
  • triple A ring made of 6 triple A motifs
  • linker
  • found in cilia & cytoplasm
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17
Q

What is the Dynein power stroke?

A

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

18
Q

What are MAPS?

A

microtubule associated proteins

19
Q

Whats is TAU protein?

A

disease protein
mainly in axons
stabilises microtubules

small amount in DNA suggesting nuclear function

20
Q

How is binding of TAU to microtubules regulated?

A

by phosphorylation

TAU affinity for MTs decreases when hyper-phosphorylated

21
Q

What is Spastin?

A

disease protein

severs stable regions of microtubules

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

22
Q

How is severing by Spastin stimulated?

A

polyglutamationf of C-terminal tubulin tail by TTLL6

23
Q

How are microtubules involved in mitosis?

A

form scaffold for sorting chromosomes

form spindle

dynein & kinesins involved

24
Q

How are microtubules involved in Cilia?

A

motile or immotile

motile have pair of central microtubules

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

25
Q

How are Kinesin and Dynein-2 involved in cilia?

A

traffic intra-flagellar (IFT) cargoes

build/maintain all cilia

26
Q

What are diseases associated with microtubules?

A

TUBA1A - polymcirogyria - small gyri

TUBB2B - Diffuse pachygyria - smooth brain

27
Q

How do neurons migrate in the developing brain?

A

neural progenitors in ventricular zone migrate to cortical plate

migration in cerebral cortex & hippocampus

28
Q

What do mutations in TUBA1A cause?

A

affect binding of kinesins

affect polymerisation

microlissencephaly
lissencephaly
pachygyriA
polymicrogyria

29
Q

What happens in Lissencephaly?

A
  • smooth brain
  • small head
  • mental retardation
30
Q

What are 2 common mutations in TUBA1A?

A
  • R402H
  • R264C

affect binding of proteins to MTs
reduced traficking
reduced microtubule stability

31
Q

What do mutations in kinesins cause?

A

hereditary spastic paraplegia

32
Q

What happens in hereditary spastic paraplegia?

A
  • Kif5a
  • 56 missense
  • in motor domain
  • spasticity in legs
  • kinesin movement affected
  • problems at synapses
33
Q

What are the mutations in Kif5a that causes SPG?

A

reduce velocity - N256S, K253N

reducing binding - R280S, K253N

34
Q

What diseases is TAU protein involved in?

A

Alzheimers

Progressive supranuclear palsy

Cortico-basal degeneration

dementia

parksinsonism

35
Q

What are the mutations in TAU protein?

A
  • in microtubule binding domain
  • reduced affinity for microtubules
  • aggregation

missense & splicing mutatons

36
Q

How does TAU cause disease

A

detach from microtubules

microtubule disassembly

reduced trafficking

misolocalisation to presynapse

synaptic dysfunction

37
Q

What is the synaptic dysfunction of Tau?

A

Tau recruits enzyme TTLL6

polyglutamates tubulin

Tau unbinds

Spastin recruited

severs & destabilises

38
Q

What is taxol?

A

microtubule stabilising drug

cancer treatment

induces mitotic arrest

cell death results from chromosome mis-segregation on multipolar spindles

39
Q

What is involved in ciliopathies?

A

kinesin and dynein

lots of syndromes

40
Q

What does mutation in dynein heavy chain cause?

A

PCD - primary cilia dyskinesia

altered bending of distal region

ability of dynein heavy chain to generate movement

MICR2120 Cell Biology & Disease (17 decks)

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