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Kin 3Z03 Neuromuscular Plasticity > Cell Review > Flashcards

Cell Review Flashcards

(53 cards)

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1
Q

nucleus
how many are in motoneurons
how many in muscle fiber

A
  • contains genetic info for proteins which carry out cell functions
    motoneuron has 1 in the cell body
    muscle fibers have more than one (multinucleated)
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2
Q

where is the other 1% of DNA that’s not in the nucleus found?

A

in mitochondria - it codes for 14 proteins

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3
Q

central dogma of gene expression

A
  • DNA has coding and noncoding sequences (exons and introns)

exons code for proteins

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4
Q

codon

A

3 nucleotide sequences of RNA that code for AA

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5
Q

stages of gene expression

A
  1. transcription - RNA made from DNA
  2. RNA processing - splicing of pre-mRNA to mature mRNA
  3. transport of mRNA to cytosol from nucleus
  4. translation - mRNA into AA chain
  5. post-translational modifications - affect protein behaviour
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6
Q

sites of gene expression regulation

A
  1. transcriptional control - turned up or down
  2. processing control - regulated @ nucleus
  3. transport/export control
  4. mRNA stability control - how quickly mRNA is degraded (the longer it’s there, the greater chance it has of being translated)
  5. translational control - turned on or off
  6. post-translational control with post-translational modifications
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7
Q

promoter

A

a sequence of DNA critical for controlling transcription

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8
Q

transcription start site

A
  • everything downstream is the coding region

- everything upstream is part of basal transcription machinery

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9
Q

TATA box

A
  • the promoting region of the gene where the TATA binding protein (TBP) and transcription initiation complex bind on to
  • found immediately upstream of transcription start site
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10
Q

DNA response/control elements

A

DNA sequences found before the TATA box

  • 6-12 nucleotides long
  • bind with proteins called transcription factors (facilitate transcription and are specific to a particular DNA sequence)
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11
Q

mRNA processing

A
  • promoter region removed from pre-mRNA
  • 5’ cap added to block promoter
  • 3’ poly A tail added
  • splicing - removal of introns by spliceosome
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12
Q

2 untranslated regions remain in mature mRNA
what are they?
why do they remain there?

A

5’ untranslated region and 3’ untranslated region

- are there to ensure mRNA gets translated (targets proper region of cytosol and keeps mRNA stable until then)

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13
Q

types of substitution mutations

A

one nucleotide in, one out

  • nonsense
  • conservative missense
  • nonconservative missense
  • sense
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14
Q

nonsense mutation

A

results in premature stop codon

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15
Q

conservative missense mutation

A

results in a different AA being coded for that has similar properties as the original AA

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16
Q

nonconservative missense mutation

A

results in a different AA being coded for that has different properties that the original AA
- causes a different charge or conformation of the protein

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17
Q

sense mutation

A

a different codon results in the same AA that was originally coded for
- the lowest risk mutation

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18
Q

frameshift mutation

A
  • result of insertions, deletions and inversions (sometimes)
  • changes reading frame of a gene so changes codon sequence of everything downstream
  • everything upstream is unaffected
  • resultant protein is often degraded or useless
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19
Q

examples of inheritance

A

autosomal dominant
autosomal recessive
x-linked recessive, carrier mother
mitochondrial

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20
Q

autosomal dominant inheritance
% chance of offspring presenting clinically
example

A

one parent has a single copy of the mutated gene

  • chance of offspring presenting clinically with the affected copy is 50%
    ex. myotonic dystrophy
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21
Q

autosomal recessive inheritance
% chance of offspring presenting clinically
example

A

2 copes of the affected gene are required for offspring to have the gene so both parents would have to be carriers

  • 25% chance of offspring presenting clinically with the disease
    ex. SMA
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22
Q

x-linked recessive inheritance, carrier mother

% chance of offspring and results

Study These Flashcards
A

mutated gene is on the x chromosome. none of the other 22 autosomes are affected

  • mother is almost always the carrier
  • 50% chance of female offspring being a carrier
  • 50% chance of male offspring having the disorder
    ex. DMD
23
Q

mitochondrial inheritance

% chance of offspring presenting clinically

Study These Flashcards
A

passed from the mother always bc all mitochondrial DNA comes from the mother

  • all children to a certain extent will present clinically with mito disorder
  • if father has mito disease, there’s no chance of offspring having the disease bc his mito DNA does not get passed onto them
24
Q

monogenic

Study These Flashcards
A

a single gene results in a single disorder

ex. most mitochondrial diseases are monogenic

25
extrafusal muscle fibers
- innervated by alpha motoneurons | - generate force to move the skeleton
26
intrafusal muscle fibers
- innervated by gamma motoneurons | - modulate sensitivity of muscle spindles to stretch
27
input resistance of slow oxidative MNs
- SO MNs have higher input resistance therefore require less synaptic activation to initiate APs - will reach threshold first, based on the size principle
28
upper motorneurons (UMNs) and lower motoneurons (LMNs) and their origins
UMNs originate in motor cortex and synapse with LMNs or alpha MNs in the brainstem or ventral horn of SC - LMN synapse with skeletal muscle
29
components of a motor unit
includes the alpha MN and the muscle fibers it innervates
30
alpha motoneuron pool
represents all alpha MNs that innervate one muscle
31
motor nucleus
all of the cell bodies of motoneurons in a motor pool
32
alpha motoneuron subtypes
slow twitch (S) fast-twitch fatigue resistant (FR) fast-twitch fatiguable (FF)
33
what muscle fibres do slow twitch (S) MNs innervate
type 1 slow oxidative fibers
34
what muscle fibres do fast-twitch fatigue resistant (FR) MNs innervate
type 2a FOG fibers
35
what muscle fibres do fast-twitch fatiguable (FF) MNs innervate
type 2b, 2x, 2d FG fibers
36
how are characteristics of alpha MNs related to the muscle fibers they innervate?
they are similar morphologically
37
immunofluorescence technique
- following muscle biopsy muscle sample is frozen, sliced into cross sections - antibodies are used to identify the specificity of a molecule (they're protein specific) - goal is to identify different fiber types in a sample when the antibodies fluoresce under microscope
38
histochemical staining technique
- uses enzymes to identify proteins (instead of antibodies) - looks at enzyme activity to determine probable fibre types in a muscle sample - isn't as specific as immunofluorescence
39
criteria to identify alpha MNs
1. location - cell bodies found in ventral lateral horn of SC 2. size of cell bodies - greater than or equal to 25um (they're pretty big) - if both these criteria are met, then the cell must be an alpha motoneuron
40
what technique can be used to identify muscle fiber and spinal MU type?
immunohistochemistry/immunofluorescence
41
NeuN
a hormonal nuclei protein that identifies all neurons
42
DAPI
identifies ALL nuclei of neurons and other types of cells
43
CHAT
choline acetyltransferase - important for ACh synthesis - identifies all alpha MNs in the ventral horn
44
using neuronal tracers
- technique only done on animals to identify which MU work with what muscles - dye injected into muscle of interest and it moves up the NMJ, to the MN cell body (somata) via axonal transport - SC cross sections of motor nuclei region are found and only MNs that target muscle will stain positive for the dye - it's good to inject different coloured tracers into different limbs when looking at multiple muscles because there's a lot of overlap in motor columns in SC
45
does muscle fiber type influence MN phenotype or is it the other way around?
both can happen
46
SV2A
synaptic vesicle protein 2A - is found in axon terminals and is important for synaptic vesicle release - is found in most type 1 fibers and about half of type 2A fibers (not in type 2) so it's a good marker of more oxidative fibers
47
if we change phenotype of a muscle, does MN type also change? how do we know?
yes | - viral DNA transduction test
48
viral DNA transduction | what is it?
- used in a study to induce muscle phenotype change - an innocuous virus is injected into the muscle that has been modified to carry a specific gene sequence - virus hijacks gene machinery and adds a gene for a protein called PGC-1α
49
PGC-1α
a transcription co-activator - works and cooperates w transcription factors to cause transcription - mice that overexpress this gene develop more slow twitch oxidative fibres therefore! this protein has the ability to change muscle phenotype independently from exercises - ie this protein increases SV2A levels in αMNs
50
viral DNA transduction technique | results of this experiment?
- a small green fluorescent protein (GFP) is associated with PGC-1α virus so that wherever the virus is taken up, will fluoresce green - we saw that PGC-1α was effective in creating type 1 fibers - to see if more type 1 MNs were present, we tested for SV2A in NMJ - it was there results: if we have phenotype change to more type 1 fibers, we want to see more SV2A which would indicate a change to more type 1 MUs
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Kin 3Z03 Neuromuscular Plasticity (5 decks)

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