Microtubule and molecular motors

Question 1

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

Answer 1

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

Question 2

What do cytoskeletal structures form?

Answer 2

Tracks that components are trafficked along

Question 3

What do molecular motors do?

Answer 3

Trafficking

Question 4

What 3 fibrillar elements make up the cytoskeleton?

Answer 4

Microtubules
Neurofilaments
Microfilaments

Question 5

What makes up microtubule walls?

Answer 5

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

Question 6

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

Answer 6

Plus ends

Question 7

How are MTs formed in dendrites and axons?

Answer 7

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

Question 8

Where are MTs less regularly aligned?

Answer 8

Dendrites

Question 9

What is MT treadmilling?

Answer 9

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

Question 10

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

Answer 10

GTP hydrolysis

Question 11

What is dynamic instability?

Answer 11

Individual microtubules alternate between cycles of growth and shrinkage

Question 12

What determines dynamic instability?

Answer 12

Rate of tubulin addition relative to rate of GTP hydrolysis

Question 13

What post-translational modifications do some MT regions undergo?

Answer 13

acetylation of alpha tubulin
Phosphorylation of beta tubulin

Question 14

What do microtubule-associates proteins do?

Answer 14

Bind to MT surfaces and alter their assembly and stability

Question 15

What do high molecular weight MAPs have?

Answer 15

Distinct localizations

Question 16

What do tau proteins do?

Answer 16

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

Question 17

What happens in Alzheimer’s disease with tau proteins?

Answer 17

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

Question 18

What are neurofilaments (NF) main function?

Answer 18

Provide structural support for the axon and regulate axon diameter

Question 19

How are NFs formed?

Answer 19

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

Question 20

What causes NFs to be disrupted in Alzheimers?

Answer 20

Lesion called neurofibrillary tangle

Question 21

How are microfilaments formed?

Answer 21

2 strands of polymerised actin monomers and are polar

Question 22

How are microfilaments dynamics regulated?

Answer 22

Treadmilling

Question 23

Where are microfilaments most abundant in neurons?

Answer 23

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

Question 24

What 4 proteins are associated with microfilaments?

Answer 24

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

Question 25

What 3 families of proteins are molecular motors derived from?

Answer 25

Kinesin Dynein Myosin

Question 26

What are the 3 differences of molecular motors?

Answer 26

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

Question 27

What are 3 common features of molecular motors?

Answer 27

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

Question 28

What does Kinesins' heavy chain consist of?

Answer 28

ATP and MT binding domains

Question 29

What do kinesins move towards?

Answer 29

Plus end of MTs

Question 30

What is the most common kinesin expressed in the brain?

Answer 30

Kinesin-1

Question 31

What causes Kinesin movement?

Answer 31

ATP hydrolysis

Question 32

What do mutations in KIF1B cause?

Answer 32

Hereditary neuropathy Charcot-Marie-Tooth

Question 33

What 2 dyneins make up the dynein superfamily?

Answer 33

Cytoplasmic and cilary dyneins

Question 34

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

Answer 34

ATP and MT

Question 35

What is dynein's function?

Answer 35

Mediate cellular transport by ATP hydrolysis

Question 36

In what direction do dyneins move?

Answer 36

Minus end of MT

Question 37

What important associated protein complex does cytoplasmic dynein have?

Answer 37

Dynactin

Question 38

What does Dynactin do?

Answer 38

Regulates dynein activity and cargo binding capacity

Question 39

What does loss of cytoplasmic dynein cause?

Answer 39

Disrupts neuronal trafficking and degeneration of motor neurons

Question 40

What is myosin's function?

Answer 40

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

Question 41

What do myosin's heavy chain consist of?

Answer 41

ATP binding site

Question 42

What regulates motor function in myosin?

Answer 42

Divergent light chains

Question 43

What do myosins use to move components along actin?

Answer 43

Energy from ATP hydolysis

Question 44

What is axonal transport processes crucial for?

Answer 44

Neuronal development, plasticity and degeneration

Question 45

What transport is slow transport?

Answer 45

Anterograde transport

Question 46

What transport is fast transport?

Answer 46

Anterograde and retrograde transport

Question 47

What does slow component a move?

Answer 47

Cytoskeletal elements as polymers

Question 48

What type of movement does slow component a exhibit?

Answer 48

Discontinuous movement

Question 49

What does slow component b move?

Answer 49

soluble enzymes and cytoskeletal proteins

Question 50

What is slow component b a rate limiting component of?

Answer 50

Nerve growth or regeneration

Question 51

What is fast anterograde transport?

Answer 51

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

Question 52

What does fast anterograde transport provide?

Answer 52

Newly synthesized components to synapses

Question 53

What needs the material transported by fast anterograde transport?

Answer 53

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

Question 54

What does fast retrograde transport move?

Answer 54

larger and more heterogeneous MBOs

Question 55

Where is fast retrograde transport thought to transport material to?

Answer 55

Material to be delivered to lysosomes eg. Growth factors

Question 56

How does size affect rate of transport?

Answer 56

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

Question 57

How is coordination of opposing motors regulated?

Answer 57

Phosphorylation of motor proteins or their cargoes

Question 58

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

Answer 58

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