Lecture 1: Neuronal organelles and their function Flashcards

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1
Q

How many synapses are there? (if we look at the count of 86 billions neurons)

A

1 * 10^15 synapses (the synapse can carry out tasks and decisions without the need of the soma as this is too far from it)

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2
Q

Which challenges do neurons face?

A

1.How to get to the right place in the brain
2.With whom to make contact
3.How to generate and maintain polarization
4. How to supply distant synapses with proteins & lipids
5. How to maintain energy levels in distant synapses
6. How to respond to changes in local environment and activity

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3
Q

Earlier was thought all neurogenesis was in embryogenesis, why is this not true?

A

In the hippocampus, in later stages of life there is still neurogenesis.

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4
Q

How do synaptic versicles travel?

A

After filling with transmitters, synaptic vesicles are moved to the active zone of the presynaptic plasma membrane by a translocation process that may be either diffusion-limited or dependent on molecular motors.

Synaptic vesicles from from an axon and should not go into dendrites but into the axon. These vesicles fuse at the presynaptic terminal at the position of the active zone.

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5
Q

What does synapse function require?

A

Energy, proteins and lipids.

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6
Q

What happens in priming and docking

A

Vesicles are primed, or docked, with a large supramolecular complex around a core assembled SNARE complex, awaiting calcium influx to trigger fusion.

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7
Q

Why are the postsynaptic density darker coloured?

A

Because all the receptors are located there.

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8
Q

What for function are microdomains characterized with?

A

These microdomains play a crucial role in organizing signaling events in polarized cells like neurons, essential for neuronal processes such as differentiation, synapse formation, and neurotransmission.

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9
Q

What happens in the axon initial segment?

A

In this place, AP are generated but it also acts as a barrier for proteins that have to go into the dendrite and not go in the axon.It thus makes sure nerons are polarized and stay polarized.

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10
Q

What does the neuromuscular junction have or is characterized with?

A

NJ has a lot of organelles and mitochondria.

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11
Q

How many active zones does Neuromuscular Junction have?

A

This synapse has two active zones. In your brain synapses, you have often only one active zone while in the NJ, there are two which is important because of their high-release probability, more versicles can fuse and be released for a longer time.

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12
Q

The synapses in the hippocampus, with only ….

A

one active zone

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13
Q

What is the Zip-code?

A

These sequences of neucleotides, or what scientists refer to as RNA “Zip-codes” are recognized by proteins that act like mail carriers and deliver RNAs to where they are supposed to go.

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14
Q

What is the SER generally used for?

A

The creation/storage of lipids and steroids

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15
Q

What is the function of the RER?

A

RER plays a significant role in the synthesis of various proteins.

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16
Q

What are the posttranslational modifications in the golgi?

A

Glycosylation and sorting for transport

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17
Q

What are the major organelles required for neuron and synapse function?

A

The mRNA leaves the nuclear envelope and is then translated and migrates into the ER.
Transmembrane proteins are formed in the ER and leave in vesicles via the ER exit sites. They
then pass the ER Golgi intermediate complex (ERGIC) and then go into the Golgi. In the Golgi,
the proteins mature a bit more but they are still immature and are glycosylated with
posttranslational modification. Then they will enter the TGN where they are sorted
(constitutive release; …). On their way to the plasma membrane, they will mature: and will
contain the proteins needed to fuse with the membrane (SNARE). This was believed until 10
years ago.

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18
Q

What is the organization of Cellular Secretory Organelle: ER

A
  • continuous network in soma, dendrites & axon
  • Present in pre- & postsynaptic terminals
  • Allows local protein translation → They think that one synapse will become very active,
    however, they do have a low lifetime (they do not go to the Golgi)
  • Major calcium store
  • Major lipid source (one big lipid bilayer
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19
Q

The SER is seen as the working protein that translates. Is this true?

A

No, RER is the one.

20
Q

In the axon, there is SER which are lipid structures that are very dynamic helped by ER-shaping proteins. Is this true?

A

Yes

21
Q

What does the ER supplies?

A

calcium to the mitochondria to make ATP via contact sites.

22
Q

There are contact sites with the plasma membrane to supply the membrane with
plasma lipids and also to get more calcium into the ER. Is this True?

A

Yes

23
Q

Where does the calcium comes from in the presynaptic terminal?

A

The calcium comes in from the plasma membrane.

24
Q

Lysosomes need prolonged calcium release to fuse? True or False

A

True

25
Q

What is the role of ERGIC?

A

Receives COPII-coated vesicles from ER (to Golgi)
- Receives COPI-coated vesicles from Golgi (to ER)
- Role in folding and quality control nascent proteins
- Role in glycosylation of proteins
(Organelle that is a combination of the ER and Golgi (might
play a replacing role of the Golgi in neurons))

26
Q

What are the characterizations of the Golgi?

A
  • Mainly present in soma (GOs in some dendrites)
  • Main organelle for post translation modifications (e.g.
    glycosylation)
  • Main organelle for sorting cargo
  • Three subzones: cis (GM130), medial (ManII), and trans
    (TGN38)
27
Q

What are the two ideas on how vesicles pass the Golgi?

A
  • The Golgi plaques mature and move
  • The vesicles go through the plaques and mature while the plaques stay in their place
28
Q

Why is the Golgi-dependent and Golgi-independent secretory routes in dendrites important?

A

There is evidence for local translocation of mRNA.

29
Q

Can we make fully glycosylated proteins in the axon?

A

No not fully due to half-life of these
proteins.

30
Q

How does the neuron transport locally made membrane proteins?

A

Membrane proteins
can only be translated in a vesicle.

31
Q

Locally translated proteins like transmembrane proteins act without the Golgi, thus there is
no glycosylation. Is this true?

A

True

32
Q

Transmembrane proteins require a vesicle to be transported to the plasma membrane. Is this true?

A

True

33
Q

What is the function of the RUSH system?

A

The RUSH system visualizes the transport of a fluorescent protein from the ER through the
Golgi to the plasma membrane.

34
Q

Give us the meaning of RUSH, the abbreviation and what HOOK is?

A

RUSH is Based on Streptavidin-Biotin Interaction
RUSH: Retention Using Selective Hooks
Hook: a protein localized to ER or Golgi tagged with streptavidin (you can target any
organelle)
Reporter: a protein of interest (X) tagged with streptavidin-binding peptide (SBP)
By the addition of biotin, SBP-X will get loose from streptavidin allowing the SBP-X to travel
away from the ER, it allows time in the secretory pathway

35
Q

How much does the brain consumes of energy?

A

The brain consumes ± 20% of energy budget

36
Q

What are the energy demanding processes in mitochondria?

A
  • Maintaining ion gradient
  • Transport
  • Synapse assembly/maintenance
  • SV refilling & recycling
  • Calcium homeostasis (when it comes in it also should be removed again)
37
Q

ATP generation at presynaptic terminals
* Glucose is the main energy source to generate ATP
* Synapses consume ± 15% of neuronal ATP
A. Both are untrue
B. Both are True
C. I is True, II is not True
D. II is True, I is not True

A

C
- Glucose is the main energy source to generate ATP
- Synapses consume ± 55% of neuronal ATP

38
Q

Glycolysis makes that much ATP

A

False

39
Q

The pyruvates are way more important than Glycolysis because
those are transported to the mitochondria where a lot of ATP is made.

A

True

40
Q

What are the two ways to attract mitochondria? (extensive explanation)

A
  1. If the synapse is active and requires a lot of energy it attracts and recruits
    mitochondria to the pre-synaptic and post-synaptic sites.
  2. The remodelling of mitochondria (influenced by calcium signalling) will attract more
    mitochondria to the presynaptic terminal which is essential to provide the synapse
    with energy.
    - But also glutamate transporters are dynamic and they are also recruited to synapses which
    provide a higher income of glucose.
41
Q

What is Autopaghy?

A

Mainly organelles or big clusters of proteins)→ to get rid of organelles by
engulfing them after which they will be degraded in lysosomes. All proteins that regulate autophagy, mutations in those, are fatal?

42
Q

What is the Endolysosomal pathway?

A

(mainly proteins)→ Local endocytosis that does not lead to
degradation (like the refilling of a synaptic vesicle with neurotransmitters after being used
already). Sometimes when the vesicle is old it escapes the cycle and is engulfed by the
proferty system where a double membrane will be around the synaptic vesicle where the
autophagosome will be fused with the lysosome

43
Q

Which is true?
- Lysosomes are terminal degradation hubs
- Proteostasis is essential for neuronal survival
- Early and late endosomes have different RED proteins expressed on their membrane.

A

All three are true

44
Q

Autophagy: degrades dysfunctional organelles and protein aggregates
Is this TRUE

A

True

45
Q
A
46
Q
A