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
Q

What will happen if more binding sites are filled with Ca?

A

The higher the probability that there will be a change of conformation and act

26
Q

How many Ca binding sites does Synaptotagmin have?

A

5

27
Q

What is Complexin?

A

A small protein

28
Q

What is the function of Complexin and where is it found?

A

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
Q

Describe the 7 events in vesicle fusion

A
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
Q

Name some diseases that affect the pre synaptic terminal and what do they affect?

A

They interrupt neurotransmission by breaking down SNARE complexes

Botox
Tetris toxin- cleaves Synaptobrevin not allowing neurotransmitter release

31
Q

What are Clathrins?

A

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
Q

What is needed to cleave the vesicle away from the membrane after exocytosis? And what are their functions?

A

Clathrin-induces curvature of the membrane

Dynamin- Causes the pinching off