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ANAT 242 > L10 (C2) > Flashcards

L10 (C2) Flashcards

1
Q

why do neurons have a unique shape and size

A

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

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2
Q

what are the 2 Microtubule Associated Proteins (MAPs) we learnt about

A

MAP2 and Tau

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3
Q

what is the role of Microtubule Associated Proteins (MAPs)

A

stabilising these structures to form parallel networks

Loss of MAPs -> tangled microtubules – disrupts structure

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4
Q

what is fast axonal transport

A

it is bidirectional (250-400 mm/day)

not quite an arm wingspan

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5
Q

what is slow axonal transport

A

anterograde/retrograde

done with the use of motor proteins and transports something by 1mm/day

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6
Q

anterograde axonal transport is moving what things in what direction

A

mitochondria,

vesicles, membrane lipids down the axon

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7
Q

Retrograde axonal transport is moving what things in what direction

A

used materials back to the soma

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8
Q

what motor protein is used for Retrograde axonal transport

A

dynein

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9
Q

what motor protein is used for anterograde axonal transport

A

kinesin

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10
Q

a motor protein has 2 domains. what are these

A

Motor domain

Tail domain

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11
Q

what does the motor domain of a motor protein control

A
  • Contains ATPase
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12
Q

what does the tail domain of a motor protein control

A
  • Specifies function

of motor molecule as it attaches onto the organelle or vesicle

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13
Q

across different species what can be said about the motor and tail domains of a motor protein

A

motor = Conserved across species

tail = Diverse within/across species

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14
Q

what is cargo

A

when something is put in a vesicle it becomes cargo

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15
Q

why do cargo have distinct mechanisms

A

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

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16
Q

what are vesicles transported along

A

microtubules

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17
Q

what is the diameter of a neurofilament

A

10nm

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18
Q

what is the predominant cytoskeletal component in a neuron

A

neurofilaments

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19
Q

what gives neurofilaments their huge tensile strength

A

associated proteins from extensive cross linking which gives it high tensile strength

therefore cross linking proteins

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20
Q

which is the most stable of the cytoskeletal components

A

neurofilaments

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21
Q

are neurofilaments able to be transported down microtubules

A

yes

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22
Q

what are microfilaments made up of

A

soluable actin in the cytoplasum

Actin binding proteins such as –filamentous (F) and monomeric (G)

it is a helical structure with week covalent bonds

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23
Q

what is the diameter of microfilaments

A

3-5nm

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24
Q

are microfilaments dynamic or static

why

A

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

25
Q

what is another name for the +ive and -ive ends of microfilaments

A

+ive = (barbed) ends

-ive = (pointed) ends

26
Q

what is treadmilling

A

a dynamic turnover of actin filaments while filament length is maintained

27
Q

how many states does actin dynamics have…. what are they

A

2

elongation and steady state

28
Q

describe the elongation state in actin dynamics

A

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)

29
Q

describe the steady state in actin dynamics

A

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

30
Q

describe the process which causes treadmilling

A

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)

31
Q

what is Treadmilling useful for

A

Treadmilling is good for cell motility as actin wants to move without changing its shape

32
Q

describe actin filament assembly

A

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

33
Q

where would you find actin F

A

in a mature neuron

G actin is the monomer (floating around in the cytoplasm) and F actin is the actin filament

34
Q

what is the main role of F actin

A

stabilisation

35
Q

other than stabilisation, what are the other roles of the actin filament (microfilament)

A

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

36
Q

where are microfilaments enriched

why

A

enriched at synapse, (pre and post)

because of shape, size and holding proteins

37
Q

what is the role of microfilaments in neuron development/plasticity

A

´Neurite formation, extension, branching, development

of spines and synapses

38
Q

what are the different types of actin networks

A

actin bundles

mesh like actin

actin gels

39
Q

what forms the different F-actin networks

A

crosslinking proteins

40
Q

what is periventricular heterotopia

A

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

41
Q

when do symptoms of periventricular heterotopia become more prominent

why

A

during teenage years because of synaptic pruning

this happens because we may be able to compensate, but when pruning happens the illness is exposed

42
Q

what is actin important for in the dendritic spines

A

MT cant get into the head of the spine

Therefore it is important for maintaining structure, shape and transport in the spines

43
Q

describe actins role at the presynaptic terminal

A

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

44
Q

where is the releasable pool held

A

in the actin network

45
Q

where is the readily releasable pool held

A

held in place at the membrane by actin

46
Q

describe actin in the postsynaptic terminal

A

Submembranous actin network

interlinks scaffolding
protein

it is the postsynaptic density

47
Q

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

what are they seen as

A

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

48
Q

what is Diabetic neuropathy

A

it is impairment to axonal transport because of high glucose levels

note that this is slow acting

49
Q

there are several alterations can contribute to the disruption of
axonal transport. what are these

A

alterations to the…

  • cytoskeleton
  • molecular motor proteins
  • cargo proteins
  • mitochondrial transport and other transport
  • and possibly, microglia-driven neuroinflammation
50
Q

what causes Diabetic neuropathy

A

Hyperglycaemia in diabetes

Excess glucose molecules allow addition of sugar molecules to protein,

51
Q

what is the effect of glycosylation if tubulin in the CNS

A

e. g. to tubulin and alters its function (seems to be a peripheral axonal tubulin effect, not
central. )

52
Q

what is affected by Diabetic neuropathy

A

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)

53
Q

Diabetic neuropathies affect on microtubules

A

leads to a ……

  • decrease in tubulin mRNA
  • increase in tubulin glycosylation
  • increase in Tau phosphorylation
  • Tau cleavage
54
Q

Diabetic neuropathies affect on microfilaments

A

increase in actin glycosylation

55
Q

Diabetic neuropathies affect on neurofilaments

A

leads to a ….

  • decrease in NF-L and NF-H mRNA (NF stands for neurofilament)
  • increases in phosphorylation leading to a loss in neurofilaments
56
Q

what is the overall effect of Diabetic neuropathy

A

decrease in….

  • axon caliber
  • speed of conduction
  • axonal transport
  • nerve regeneration
57
Q

AD can be described as

A

Progressive unrelenting decline in cognition

58
Q

how long can the preclinical phase (before you get diagnosed) of AD be

A

up to 30 years

by the time you see symptoms the decline is very quick

ANAT 242 (17 decks)

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