L10 (C2) Flashcards
why do neurons have a unique shape and size
We need the viable shapes because of the input coming into the cell, where they are located and where they have to transmit that information
what are the 2 Microtubule Associated Proteins (MAPs) we learnt about
MAP2 and Tau
what is the role of Microtubule Associated Proteins (MAPs)
stabilising these structures to form parallel networks
Loss of MAPs -> tangled microtubules – disrupts structure
what is fast axonal transport
it is bidirectional (250-400 mm/day)
not quite an arm wingspan
what is slow axonal transport
anterograde/retrograde
done with the use of motor proteins and transports something by 1mm/day
anterograde axonal transport is moving what things in what direction
mitochondria,
vesicles, membrane lipids down the axon
Retrograde axonal transport is moving what things in what direction
used materials back to the soma
what motor protein is used for Retrograde axonal transport
dynein
what motor protein is used for anterograde axonal transport
kinesin
a motor protein has 2 domains. what are these
Motor domain
Tail domain
what does the motor domain of a motor protein control
- Contains ATPase
what does the tail domain of a motor protein control
- Specifies function
of motor molecule as it attaches onto the organelle or vesicle
across different species what can be said about the motor and tail domains of a motor protein
motor = Conserved across species
tail = Diverse within/across species
what is cargo
when something is put in a vesicle it becomes cargo
why do cargo have distinct mechanisms
to select and dock to the correct motor
protein tail
The protein are are on the vesical are like sign posts/labels which tell the vesical where to go (where it is required)
This is highly organised
what are vesicles transported along
microtubules
what is the diameter of a neurofilament
10nm
what is the predominant cytoskeletal component in a neuron
neurofilaments
what gives neurofilaments their huge tensile strength
associated proteins from extensive cross linking which gives it high tensile strength
therefore cross linking proteins
which is the most stable of the cytoskeletal components
neurofilaments
are neurofilaments able to be transported down microtubules
yes
what are microfilaments made up of
soluable actin in the cytoplasum
Actin binding proteins such as –filamentous (F) and monomeric (G)
it is a helical structure with week covalent bonds
what is the diameter of microfilaments
3-5nm
are microfilaments dynamic or static
why
dynamic because there is remodelling of actin filaments continually
this is able to happen from both ends and is needed as actin needs to be able to change its shape as it is critical to the neurons function
what is another name for the +ive and -ive ends of microfilaments
+ive = (barbed) ends
-ive = (pointed) ends
what is treadmilling
a dynamic turnover of actin filaments while filament length is maintained
how many states does actin dynamics have…. what are they
2
elongation and steady state
describe the elongation state in actin dynamics
it is when the microfilament is growing
at adds actin to both the +ive and -ive end (but actin is added faster to the +ive end)
describe the steady state in actin dynamics
The steady state is when actin stays the same length. It polymerised at one end and depolymerises at the other. It does this with ATP.
This is called treadmilling
describe the process which causes treadmilling
G actin is bound to ATP but when it binds to the actin filament, ATP is hydrolysed to ADP which is much easier to be depolymerised (at the other end from where it bound)
what is Treadmilling useful for
Treadmilling is good for cell motility as actin wants to move without changing its shape
describe actin filament assembly
actin is bound to an ATP molecule in the cytoplasm
eventually there will be spontaneous nucleation (which is when 3 actin molecules come together) which forms a 3 actin nucleus
At the pointed end you have the addition of the actin molecules much faster than at the -ive end
ATP hydrolysis is happening turning into ADP. This is what causes treadmilling
where would you find actin F
in a mature neuron
G actin is the monomer (floating around in the cytoplasm) and F actin is the actin filament
what is the main role of F actin
stabilisation
other than stabilisation, what are the other roles of the actin filament (microfilament)
inner plasma membrane proteins crosslink to actin
anchors molecules and vesicles (very organised)
in dendritic spine head there are no MTs because they are too big. therefore in the spine heads actin filaments maintain the shape
where are microfilaments enriched
why
enriched at synapse, (pre and post)
because of shape, size and holding proteins
what is the role of microfilaments in neuron development/plasticity
´Neurite formation, extension, branching, development
of spines and synapses
what are the different types of actin networks
actin bundles
mesh like actin
actin gels
what forms the different F-actin networks
crosslinking proteins
what is periventricular heterotopia
it is a mutation in an actin associated protein which causes neurons do not migrate properly during the early
development of the fetal brain leading to things like seizures and cognitive troubles
when do symptoms of periventricular heterotopia become more prominent
why
during teenage years because of synaptic pruning
this happens because we may be able to compensate, but when pruning happens the illness is exposed
what is actin important for in the dendritic spines
MT cant get into the head of the spine
Therefore it is important for maintaining structure, shape and transport in the spines
describe actins role at the presynaptic terminal
actin is enriched at presynaptic terminal
as it regulates the vesicle pool
(idk what this means - Small groups linked
´Groups attached to plasma membrane)
actin could also be Involved in vesicle recycling at the periactive zone
where is the releasable pool held
in the actin network
where is the readily releasable pool held
held in place at the membrane by actin
describe actin in the postsynaptic terminal
Submembranous actin network
interlinks scaffolding
protein
it is the postsynaptic density
Defects in axonal transport and/or in the cytoskeleton are often seen in the CNS and peripheral neuropathies.
what are they seen as
main ones
- Alzheimer’s disease
- Motor neuron disease
- Parkinson’s disease
Acquired peripheral neuropathies
Diabetic neuropathies
Metabolic syndromes
Auto-immune diseases
Alcohol abuse
Anti cancer therapies
what is Diabetic neuropathy
it is impairment to axonal transport because of high glucose levels
note that this is slow acting
there are several alterations can contribute to the disruption of
axonal transport. what are these
alterations to the…
- cytoskeleton
- molecular motor proteins
- cargo proteins
- mitochondrial transport and other transport
- and possibly, microglia-driven neuroinflammation
what causes Diabetic neuropathy
Hyperglycaemia in diabetes
Excess glucose molecules allow addition of sugar molecules to protein,
what is the effect of glycosylation if tubulin in the CNS
e. g. to tubulin and alters its function (seems to be a peripheral axonal tubulin effect, not
central. )
what is affected by Diabetic neuropathy
impaired cytoskeletal assembly
decrease in axon caliber
motor proteins fail to bind to microtubules leading to impaired transport of synaptic vesicles and mitochondria
neuroinflammation
Microglial cells-proinflammatory
molecules (TNF)-affect anterograde transport
(NNF causes inflammation as an immune response)
Diabetic neuropathies affect on microtubules
leads to a ……
- decrease in tubulin mRNA
- increase in tubulin glycosylation
- increase in Tau phosphorylation
- Tau cleavage
Diabetic neuropathies affect on microfilaments
increase in actin glycosylation
Diabetic neuropathies affect on neurofilaments
leads to a ….
- decrease in NF-L and NF-H mRNA (NF stands for neurofilament)
- increases in phosphorylation leading to a loss in neurofilaments
what is the overall effect of Diabetic neuropathy
decrease in….
- axon caliber
- speed of conduction
- axonal transport
- nerve regeneration
AD can be described as
Progressive unrelenting decline in cognition
how long can the preclinical phase (before you get diagnosed) of AD be
up to 30 years
by the time you see symptoms the decline is very quick
