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ANAT242 > Lecture 11- Cell Biology of Neurons 1 > Flashcards

Lecture 11- Cell Biology of Neurons 1 Flashcards

1
Q

What is the shape of a purkinje cell like and why?

A
  • Has a massive dendritic tree as it listens to a whole bunch of inputs
  • This links to it’s function as it smooths out signals leading to fine muscle control/ coordination (found in the cerebellum)
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2
Q

What are the three components of the cytoskeleton?

A
  • Tubulin (tubulin molecules)
  • Neurofilament (intermediate filament)
  • Microfilament (F- actin, G-actin)
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3
Q

Describe the various layers/ components of the neuronal cytoskeleton…

A
  • Membrane composed of lipids
  • Microtubules run down middle- microtubule cross-linkers stabilize (connect the microtubules together)
  • Neurofilaments + F-actin run along outside
  • Spectrins adhere to membrane + cytoskeleton (causes rigidity)
  • Adducin links everything together
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4
Q

How is material transported down an axon?

A
  • Via the microtubules.

- Called axonal transport or trafficking

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5
Q

How was axonal transport experimentally shown?

A
  • Ligate the axon (tie it off) preventing movement of materials that would usually travel from the cell body down the axon
  • Can tell that they haven’t because of build up/ labelling in the soma
  • APP was used to show this as it is made in the soma and travels down in the anterograde direction down the axon. When ligation occurred APP built up on the proximal side (before ligation)
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6
Q

What two ways can material travel down the axon?

A
  • Anterograde= from cell body down axon towards nerve terminal (starting at the proximal end). Typically mitochondria, vesicles, membrane lipids
  • Retrograde= From nerve terminal backwards to the cell body (starting at the distal end). Typically used material/waste.
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7
Q

What are microtubules like?

A

-20-28nm diameter

-Hollow tube of protein tubulin:
• Made of dimers –⍺/ß tubulin
• Soluble tubulin (⍺/ß) in cell
• Polarized molecule, +/– end

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8
Q

How are microtubules elongated?

A
  • Add tubulin dimers at + end to elongate (create axon)

- Labile – de- or re-polymerize as needed

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9
Q

What drives the de- or re-polymerization of axons?

A
  • GTP bound to β-Tubulin (phosphate groups are the cellular energy currency)
  • GTP goes to GDP to cause polymerization (extra phosphate group attaches to dimers). Islands stabilize the growing microtubule.
  • When dimers lose the phosphate group (happens with time) catastrophe occurs and the microtubule dissociates from itself as there is no longer a force driving depolarization
  • Rescue factors bind to microtubule in an attempt to hold it together
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10
Q

What happens when microtubules break down/ depolymerize?

A

Axonal transport can longer occur. Get break down in functioning.

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11
Q

What does MAP stand for and what do they do? What is the ideal case for microtubule growth?

A
  • MAP= microtubule associated protein
  • Stabilize microtubules meaning they can grow longer
  • Ideal case is when have TPX2 (microtubule nucleation factor found near nucleation site), TOG (also helping with polymerization) and TuRC (a nucleation site formed by the action of GCPs)
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12
Q

What is MTOC?

A

Microtubule organisation complex: invovled in tethering as the microtubules grow

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13
Q

How does the orientation of microtubules differ between an axon and dendrite + why?

A
  • Axon= uniform orientation + end towards axonal end (as only grow in one way)
  • Dendrite= mixed orientation of microtubules as dendrites branch in many directions
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14
Q

Where is the Golgi apparatus? Where are the Golgi outposts?

A
  • Golgi apparatus in the axon near the soma/ cell body. Proteins are packaged for axonal transport down the microtubules
  • Golgi outposts at the branches of the dendrite
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15
Q

What does the MAPs tau + MAP2 do?

A
  • Links one microtubule to the next creating a rigid organised structure (highway for axonal transport)
  • Stabilize
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16
Q

How do Tau and MAP2 differ in terms of their location?

A
  • Tau found mainly in the dendrite and axon including the distal axon
  • MAP2 is found in the soma and dendrite (specific)
17
Q

What happens when the MAPs are lost/ malfunction?

A

-The microtubules tangle and get a disruption of the structure

18
Q

What do GCPs do?

A

-Bind to gamma tubulin to provide a nucleation site (TuRC =
Gamma Tubulin Ring Complex)
-A nucleation site is a place for things to bind allowing for microtubule growth/ polymerization

19
Q

When microtubules are growing what happens after the minimum stable microtubule seed is reached?

A

Get rapid microtubule growth

20
Q

What are centrosomes?

A

Found in soma, bunch of microtubules anchor to it.

21
Q

What does pectin do?

A

Links microtubules to intermediate filaments

22
Q

How does fast and slow axonal transport differ?

A

-Fast axonal transport: bidirectional (250-400 mm/day)

-Slow axonal transport: anterograde (1 mm/day)
• uses motor proteins: Kinesin - anterograde, Dynein – retrograde

23
Q

How does cargo ‘know’ which motor protein to dock to in order to be transported where it needs to go?

A
  • Motor proteins have a cargo domain which expresses a bunch of different proteins and this is how they recognize each other (specify)
  • This prevents transport of things that are not meant to be transported
24
Q

Which out of the motor domain and tail domain is conserved or diverse across species?

A
  • Motor domain= Contains ATPase, Conserved across species (is what binds to the microtubule)
  • Tail domain= Specifies function of motor molecule, binds to specific cargoes (e.g. vesicle) therefore diverse within/ across species
25
Q

How do motor proteins walk?

A
  • Use universal cellular energy (ATP)

- Convert chemical potential (Phosphate) to mechanical energy

26
Q

What are neurofilaments (size, structure, function)?

A
  • Smaller than microtubules (~10 nanometers)
  • Predominant cytoskeletal component = intermediate filaments
  • huge mechanical strength
  • most stable of cytoskeleton
  • important in structural framework
  • have associated proteins which are invovled in extensive cross linking giving them their high tensile strength.
27
Q

What are the three major components of neurofilaments?

A

Light, Medium, and Heavy Neurofilament Protein (NFL, NFM, NFH)

28
Q

What are microfilaments (size, structure, function)?

A
  • 3-5nm
  • Actin: filamentous (F) and monomeric (G)
  • dynamic = remodelling of actin filaments continually
    • (barbed) and – (pointed) ends
29
Q

What are the dynamics of actin like?

A

Described as actin treadmilling:

  • ATP binds to monomeric actin forming ATP-actin complex
  • Hydrolysis means lose phosphate group resulting in ADP-actin
  • After this get nucleation where the ADP-actins join together into a nucleus (spontaneous)
  • Polymerize from this point (forming chain). As this happens it breaks away at the - end by losing it’s phosphate group. This means there is a dynamic turnover of actin filaments while filament length is maintained
30
Q

What is actin when it is being carried down microtubules?

A

A cargo

31
Q

What does actin do?

A
  • Stabilizes the end of the synaptic bouton allowing for exocytosis and endocytosis
  • Enriched at presynaptic terminal regulating vesicle pool. Small groups linked. Groups attached to plasma membrane
  • At periactive zone might be involved in vesicle recycling
  • In dendritic spines sticks at the end of active polymerization zone allowing growth
32
Q

What happens when axonal transport goes wrong?

A

Defects in axonal transport and/or in the cytoskeleton are often seen in the CNS and peripheral neuropathies:

Seen in
• Alzheimer’s disease
• Motor neuron disease
• Parkinson’s disease
Acquired peripheral neuropathies
• Diabetic neuropathies
• Metabolic syndromes
• Auto-immune diseases
• Alcohol abuse
• Anti cancer therapies
33
Q

What is happening in Alzheimer’s disease (what MAP is invovled)?

A
  • Tau protein stabilizes microtubules
  • Phosphorylated Tau dissociates from microtubule – microtubule depolymerizes
  • Phosphorylated Tau forms aggregates creating neurofibrillary tangles
  • These tangles are associated with Alzheimer’s.

ANAT242 (25 decks)

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