Lecture 11- Cell Biology of Neurons 1 Flashcards
(33 cards)
What is the shape of a purkinje cell like and why?
- 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)
What are the three components of the cytoskeleton?
- Tubulin (tubulin molecules)
- Neurofilament (intermediate filament)
- Microfilament (F- actin, G-actin)
Describe the various layers/ components of the neuronal cytoskeleton…
- 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
How is material transported down an axon?
- Via the microtubules.
- Called axonal transport or trafficking
How was axonal transport experimentally shown?
- 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)
What two ways can material travel down the axon?
- 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.
What are microtubules like?
-20-28nm diameter
-Hollow tube of protein tubulin:
• Made of dimers –⍺/ß tubulin
• Soluble tubulin (⍺/ß) in cell
• Polarized molecule, +/– end
How are microtubules elongated?
- Add tubulin dimers at + end to elongate (create axon)
- Labile – de- or re-polymerize as needed
What drives the de- or re-polymerization of axons?
- 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
What happens when microtubules break down/ depolymerize?
Axonal transport can longer occur. Get break down in functioning.
What does MAP stand for and what do they do? What is the ideal case for microtubule growth?
- 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)
What is MTOC?
Microtubule organisation complex: invovled in tethering as the microtubules grow
How does the orientation of microtubules differ between an axon and dendrite + why?
- Axon= uniform orientation + end towards axonal end (as only grow in one way)
- Dendrite= mixed orientation of microtubules as dendrites branch in many directions
Where is the Golgi apparatus? Where are the Golgi outposts?
- 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
What does the MAPs tau + MAP2 do?
- Links one microtubule to the next creating a rigid organised structure (highway for axonal transport)
- Stabilize
How do Tau and MAP2 differ in terms of their location?
- Tau found mainly in the dendrite and axon including the distal axon
- MAP2 is found in the soma and dendrite (specific)
What happens when the MAPs are lost/ malfunction?
-The microtubules tangle and get a disruption of the structure
What do GCPs do?
-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
When microtubules are growing what happens after the minimum stable microtubule seed is reached?
Get rapid microtubule growth
What are centrosomes?
Found in soma, bunch of microtubules anchor to it.
What does pectin do?
Links microtubules to intermediate filaments
How does fast and slow axonal transport differ?
-Fast axonal transport: bidirectional (250-400 mm/day)
-Slow axonal transport: anterograde (1 mm/day)
• uses motor proteins: Kinesin - anterograde, Dynein – retrograde
How does cargo ‘know’ which motor protein to dock to in order to be transported where it needs to go?
- 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
Which out of the motor domain and tail domain is conserved or diverse across species?
- 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
