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Membrane Biology > Microtubule and molecular motors > Flashcards

Microtubule and molecular motors Flashcards

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1
Q

Why is the delivery process for proteins in neurons more complex?

A

Distance
Constant requirement for new protein components and organelles
synaptic signals and old components need to be returned to cell body for degradation

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2
Q

What do cytoskeletal structures form?

A

Tracks that components are trafficked along

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3
Q

What do molecular motors do?

A

Trafficking

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4
Q

What 3 fibrillar elements make up the cytoskeleton?

A

Microtubules
Neurofilaments
Microfilaments

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5
Q

What makes up microtubule walls?

A

13 protofilaments formed by linear arrangement of heterodimers of alpha and beta tubulin molecules

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6
Q

What end of microtubules is GTP-bound tubulin added to?

A

Plus ends

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7
Q

How are MTs formed in dendrites and axons?

A

Nucleation at MT organising centre
Then release to migrate into axons or dendrites

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8
Q

Where are MTs less regularly aligned?

A

Dendrites

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9
Q

What is MT treadmilling?

A

Dynamic behavior which tubulin molecules bound to GDP are continually lost from - end and replaced on + end

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10
Q

What weakens the binding of tubulin for adjacent molecules and causes dynamic instability?

A

GTP hydrolysis

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11
Q

What is dynamic instability?

A

Individual microtubules alternate between cycles of growth and shrinkage

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12
Q

What determines dynamic instability?

A

Rate of tubulin addition relative to rate of GTP hydrolysis

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13
Q

What post-translational modifications do some MT regions undergo?

A

acetylation of alpha tubulin
Phosphorylation of beta tubulin

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14
Q

What do microtubule-associates proteins do?

A

Bind to MT surfaces and alter their assembly and stability

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15
Q

What do high molecular weight MAPs have?

A

Distinct localizations

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16
Q

What do tau proteins do?

A

Line MT and form links with adjacent MTs - facilitates MT stabilization within cells

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17
Q

What happens in Alzheimer’s disease with tau proteins?

A

Tau is hyperphosphorylated and sequestered into neurofibrillary tangles - less tau to bind MT
MT instability and reduced axonal transport

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18
Q

What are neurofilaments (NF) main function?

A

Provide structural support for the axon and regulate axon diameter

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19
Q

How are NFs formed?

A

Fibers twist around eachother - form monomers
Monomoers form coiled-coil heterodimers
Dimers form tetrameric complex - forms protofilament
2 protofilaments -> protofibril -> 3 protofibrils -> neurofilament

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20
Q

What causes NFs to be disrupted in Alzheimers?

A

Lesion called neurofibrillary tangle

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21
Q

How are microfilaments formed?

A

2 strands of polymerised actin monomers and are polar

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22
Q

How are microfilaments dynamics regulated?

A

Treadmilling

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23
Q

Where are microfilaments most abundant in neurons?

A

Presynaptic terminals, dendritic spines and growth cones
are present in cytoplasm

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24
Q

What 4 proteins are associated with microfilaments?

A

Myosin/tropomyosin
Capping proteins - anchor
Microfilament severing proteins - reorganise actin cytoskeleton
Cross-linking proteins - bundle microfilaments

25
Q

What 3 families of proteins are molecular motors derived from?

A

Kinesin
Dynein
Myosin

26
Q

What are the 3 differences of molecular motors?

A

Can work as single molecules or large assemblies
Undergo linear motion or rotate around axis
Drive subcellular transport from a few micrometers up to a metre

27
Q

What are 3 common features of molecular motors?

A

Undergo energy-dependent conformational changes
Unidirectional movement
All consist of a dimer of 2 heavy chains with catalytic motor domains and a stalk region

28
Q

What does Kinesins’ heavy chain consist of?

A

ATP and MT binding domains

29
Q

What do kinesins move towards?

A

Plus end of MTs

30
Q

What is the most common kinesin expressed in the brain?

A

Kinesin-1

31
Q

What causes Kinesin movement?

A

ATP hydrolysis

32
Q

What do mutations in KIF1B cause?

A

Hereditary neuropathy Charcot-Marie-Tooth

33
Q

What 2 dyneins make up the dynein superfamily?

A

Cytoplasmic and cilary dyneins

34
Q

What two binding domains are present in dynein’s heavy chains?

A

ATP and MT

35
Q

What is dynein’s function?

A

Mediate cellular transport by ATP hydrolysis

36
Q

In what direction do dyneins move?

A

Minus end of MT

37
Q

What important associated protein complex does cytoplasmic dynein have?

A

Dynactin

38
Q

What does Dynactin do?

A

Regulates dynein activity and cargo binding capacity

39
Q

What does loss of cytoplasmic dynein cause?

A

Disrupts neuronal trafficking and degeneration of motor neurons

40
Q

What is myosin’s function?

A

Roles in neuronal growth and development and specialised cells (sensory hair cells of cochlea)

41
Q

What do myosin’s heavy chain consist of?

A

ATP binding site

42
Q

What regulates motor function in myosin?

A

Divergent light chains

43
Q

What do myosins use to move components along actin?

A

Energy from ATP hydolysis

44
Q

What is axonal transport processes crucial for?

A

Neuronal development, plasticity and degeneration

45
Q

What transport is slow transport?

A

Anterograde transport

46
Q

What transport is fast transport?

A

Anterograde and retrograde transport

47
Q

What does slow component a move?

A

Cytoskeletal elements as polymers

48
Q

What type of movement does slow component a exhibit?

A

Discontinuous movement

49
Q

What does slow component b move?

A

soluble enzymes and cytoskeletal proteins

50
Q

What is slow component b a rate limiting component of?

A

Nerve growth or regeneration

51
Q

What is fast anterograde transport?

A

Movement of membrane bound organelles (MBOs) along MTs away from cell body

52
Q

What does fast anterograde transport provide?

A

Newly synthesized components to synapses

53
Q

What needs the material transported by fast anterograde transport?

A

Supply and turnover of intracellular membrane compartments
Secretory products
Proteins needed for axonal metabolism

54
Q

What does fast retrograde transport move?

A

larger and more heterogeneous MBOs

55
Q

Where is fast retrograde transport thought to transport material to?

A

Material to be delivered to lysosomes eg. Growth factors

56
Q

How does size affect rate of transport?

A

Larger the size the more drag due to interactions with cytoplasmic structures

57
Q

How is coordination of opposing motors regulated?

A

Phosphorylation of motor proteins or their cargoes

58
Q

How is targeting of certain proteins to discrete regions of the neuron regulated?

A

Local changes in balance between kinase and phosphatase activity in subdomains act on motor proteins

Membrane Biology (19 decks)

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