Lecture 5.1 Flashcards

1
Q

What is the synaptic unit

A

The active zone

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2
Q

What is in an active zone?

A

The pre synaptic region continuing many vesicles
Widened electron dense intercellular space
Post synaptic density (Type 1-excitatory have a thicker post synaptic density than type 2-inhibitory)

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3
Q

How many vesicles are released per action potential?

A

Each active zone releases one or so vesicles per AP

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4
Q

How many molecules of ACh are in one vesicle in the NMJ?

A

Around 10,000 molecules

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5
Q

Why is the mossy fibre synapse stronger?

A

More current flows to the dendrite

Synapses are close to the cell body therefore there is less current leakage-the full effect is felt

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6
Q

Name the 3 vesicle pools

A

Reserve Pool-where the majority of vesicles are kept
Recycling Pool
Readily Releasable Pool-Pre docked/roughly 10 vesicles

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7
Q

What tethers recycling and reserve vesicles?

A

Actin filaments

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8
Q

Which of the 3 vesicle types can be mobilised quickly?

A

Recycling Vesicles

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9
Q

What determines the probability of vesicle release?

A

The number of pre docked vesicles
The sensitivity of the release trigger to calcium
The amount of Ca entry
The site of Ca entry

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10
Q

Name 5 surface proteins of vesicles

A

Synaptotagmin, Synapsin, Rab 3, Rab 5, VAMP

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11
Q

What is Synaptotagmin?

A

Surface protein that is the Ca trigger

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12
Q

What is Synapsin?

A

A surface protein that tethers the resting vesicles to actin
Phosphorylation allows forward movement of vesicle

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13
Q

What is Rab 3?

A

A surface protein, that targets vesicles to the docking site by binding to RIM protein

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14
Q

What is Rab 5?

A

A surface protein, important for re-uptake after exocytosis of the vesicle

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15
Q

What is VAMP(Synaptobrevin)?

A

A surface protein, vesicular SNARE protein, formation of the docking complex requires a SNARE complex

VAMP interacts with vesicular amp 3 snare proteins, forms a helix which is the docking site

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16
Q

What do all membrane fusion events require and what do they do specifically?

A

Formation of a SNARE complex (pulls the 2 membranous structures together)
A SM protein ex./Munc 18(initiates phospholipid mixing)

17
Q

What is required for vesicle docking?

A

Requires fusion of 4 SNARE protein alpha Helices (1 supplied by the vesicle, 3 supplied by plasma membrane at the synaptic terminal-2 Helices per Snap 25 protein, 1 helix per syntax in protein

18
Q

What is synaptic failure?

A

Where a vesicle is not released at the synapse

19
Q

Describe the molecular mechanisms that occur when a vesicle docks to the membrane?

A

Vesicle docks
SNARE complexes form to pull membrane together (Snaptobrevin, Syntaxin, 2 SNAP-25)
Entering Ca binds to Synaptotagmin
Ca bound Synaptotagmin catalysed membrane fusion by binding to SNAREs and plasma membrane

20
Q

What 2 proteins promote membrane bending and what do they form complexes with?

A

Munc 13 and Munc 18

With Syntaxin

21
Q

What is the main role of RIM and what does it bind to?

A

To bind key players

Binds to the vesicle, VACC and Munc 13

22
Q

All vesicular fusions occur via ………complexes

A

SNARE complexes

23
Q

Does vesicular fusion with in the cell require Ca?

A

No, only in the synapse is Ca needed

24
Q

Why does synaptic vesicle fusion need Ca?

A

Phospholipid mixing and vesicle fusion does not occur in the absence of Ca

25
What will happen if more binding sites are filled with Ca?
The higher the probability that there will be a change of conformation and act
26
How many Ca binding sites does Synaptotagmin have?
5
27
What is Complexin?
A small protein
28
What is the function of Complexin and where is it found?
It binds to SNARE complex through Synaptotagmin When SNARE complex changes conformation when Ca enters, Complexin is extracted from the SNARE complex preventing it from reaching its destination
29
Describe the 7 events in vesicle fusion
``` Docking (SNARE, RAB 3, RIM) Priming (SNARE tightens) Fusion (Ca dependent) SNARE complex dissociation (by NSF+SNAP) Endocytosis (Retrieval of empty vesicle) Re-acidification (correct pH) Neurotransmitter filling ```
30
Name some diseases that affect the pre synaptic terminal and what do they affect?
They interrupt neurotransmission by breaking down SNARE complexes Botox Tetris toxin- cleaves Synaptobrevin not allowing neurotransmitter release
31
What are Clathrins?
Are small proteins that cover the vesicle after the neurotransmitters have been released. Dynamic ring is added that pinches the vesicle off the membrane
32
What is needed to cleave the vesicle away from the membrane after exocytosis? And what are their functions?
Clathrin-induces curvature of the membrane | Dynamin- Causes the pinching off