Natalie Gardiner Flashcards
what is the order of movement of info?
synapse - dendrite - soma - axon - synapse
describe the development of neuronal polarity
Plated neurons make lamellipodia.
neurons extend several equal length minor processes.
one process beings to grow rapidly.
remaining processes grow slowly and acquire dendritic characteristics.
neurons fully polarised, synapses begin to form. (day 7-10)
very fast
describe the polarity of axons and dendrites
Axons – all microtubules oriented with Plus ends outwards, and associate with specific binding proteins to stabilise polymers
Dendrites – Mixed orientation of microtubules in dendrites
what is the cytoskeleton made of?
microtubules
microfilaments
intermediate filaments
describe microtubules
tubulin
25nm largest
hollow tubes
GTP nucleotide
describe microfilaments
actin
7nm smallest
helical filaments
ATP nucleotide
describe intermediate filaments
vimentin/neurofilaments
10nm middle
rope like filaments
no bound nucleotide
describe microtubule structure
a and b tubulin are globular proteins.
associate by non covalent bonds to form a ab heterodimer.
heterodimers join to form a protofilament.
13 protofilaments form a mature microtubule in a cylinder.
each monomer has a binding site for 1 molecule of GTP.
other binding sites for proteins/drugs.
has polarity.
- end a tubulin exposed. slow growing.
+ end b tubulin exposed. fast growing, heterodimers add to this end.
what can tubulin subunits do?
enzymes that catalyse GTP hydrolysis to GDP
how many protofilaments form a mature microtubule in a cylinder.
13
what are the forms of tubulin?
T form and D form
most free are T form.
D form has been hydrolysed
T form are recruited to the plus end.
subunits in D form shed from the minus end
what is the GTP tubulin cap?
stable, strong bond.
??
what is tradmilling.
equal number adding and being taken off.
polymer constant length
what is dynamic instability
if GTP hydrolysis is faster than subunit addition.
what is a loss of GTP cap?
everything is hydrolysed, all bonds become weaker.
curvature and shrinking.
what is a “catastophe” depolymerisation.
structure breaks down.
rescued by new GTP tubulin.
what molecules can slow down the hydrolysis to GDP and stabalise the molecules?
XMAP215, EB1 and CLIP-170
what are microtubule associated proteins (MAPs)
can be large/small.
bind to molecule, slow down GDP hydrolysis and stabilise it.
promote MT polymerisation.
also organise and anchor organelles.
what do neurofilaments dictate?
axonal diameter.
space themselves out by mutual charge repulsion of sidearms.
why is axonal diameter important?
faster the conduction rate.
myelinated axons?
where are neurofilaments added on?
along the width of the NF, as well as at the ends.
describe actin
single globular polypeptide
binding site for ATP
assemble head-tail to generate protofilaments.
unrelated to tubulin.
2 parallel protofilaments twist in a right-handed helix – to form a flexible microfilament. organised into linear bundles, particularly concentrated beneath plasma membrane.
Like MTs, actin filaments have polarity and undergo treadmilling and dynamic instability (mediated by ATP hydrolysis rather than GTP).
Actin filaments can associate with accessory proteins – to form stable, large adhesion complexes – linking internal cytoskeleton with extracellular environment.
describe the actin cytoskeleton and the growth cone.
compare to dendritic growth cones.
Actin cytoskeleton is less condensed/more dynamic in axon growth cone which allows microtubules through to drive axon outgrowth.
In contrast, dendritic growth cones have a more rigid cytoskeleton – therefore less elongation
sum the role of the neuronal cytoskeleton.
MTs confers polarity to the neuron.
MTs play a crucial role in maintaining structure and strength and organelle positioning within the cell
NFs play role in tensile strength, axonal calibre and conduction velocity.
MFs also have polarity and play active role in rapid outgrowth, growth cone dynamics and anchoring components
Dynamic remodelling of the neuron by MTs and MFs drives development, regeneration and plasticity
MT form the ‘Tracks’ for specialised delivery of proteins – ‘axonal transport’