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BISC 407 - Cellular and Molecular Neuroscience > Lecture 10 - The Active Zone > Flashcards

Lecture 10 - The Active Zone Flashcards

1
Q

Where is the active zone?

A

is an electrin dense region at the presynaptic membrane - get signal via em where very proteinacious or electron dense

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2
Q

What are the four major functions of the active zone?

A
  1. docking and priming of synaptic vesicles - docked means bring them close to the membrane and prime makes them ready for fusion molecularly
  2. recruit and stabilize voltage gated calcium channels to the presynaptic membrane - allows for fast excitation and coupling
  3. coordinate pre and post synaptic alignment through trans synaptic cell adhesion proteins
  4. mediate much of the short and long term presynaptic plasticity - either directly through secondary messengers like caclium or dag or indirectly through recruiting effects
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3
Q

What role do actuve zone play in synaptic transmission?

A

actuve role - modulate NT release and response to AP through dociking and priming anf calcium channels and transcynaptic alignment and LTP

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4
Q

What are the three major structures that the EM labels?

A
  1. synaptic vesicles
  2. dense projections like AZ proteins
  3. postsynaptic compartments
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5
Q

If you take an EM cross section at the NMj what will you see?

A

a dense projection of a T bar surrounded by synaptic vesicles

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6
Q

What is the dense projection of a c elegan like?

A

thin and wispy

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7
Q

What is the dense projection of the NMJ in fly?

A

T-bar with synaptic vesicles

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8
Q

What is seen in ribbon synapse of goldfish photorecptor?

A

many synaptic vesicles

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9
Q

What is seen in EM of central synapse?

A

underdeveloped dense projection and not many SV cause only releases like one at a time

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10
Q

What are the five evolutioanruly conserved proteins that make up the active zone?

A
  1. RIM - RAb3 interacting molecule
  2. unc13/dunc13/munc13
  3. Liprin/alpha
  4. RIM-BP
  5. ELKS
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11
Q

What is found in the actuve zone?

A

-calcium channels
-elks
-rim-bp
-rim
-liprin-alpha
-unc13/dunc13/munc13

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12
Q

What happens if you delete one active zone protein?

A

nothing much since there is great redundancy built into the system

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13
Q

Why do all of the active zone protein interact with each other via binding domains?

A

to make a stable resilient molecular scaffolding machine primed for efficent sv fusion

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14
Q

What are RIM proteins?

A

the central organziing moelcule of the active zone

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15
Q

What are the three roles of RIM?

A

-SV docking and priming
-recruit calcium channels to actuve zones
-short term plasticity

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16
Q

What domain of RIM binds to unc13 for positioning synapses for vesicle fusion aka docking and priming?

A

C2 domain

17
Q

What domain of RIM binds ELKS and calcium channels for calcium posiitoning cause elks helps with calcium channel posiitoning and how many syanptic vesicles are at atcive zone?

A

PDZ domain

18
Q

What does the zinc finger domain of RIM do?

A

takes synaptic vesicle and brings it to unc13 for priming and docking

19
Q

What else do the PDZ and C2A and C2B domains do?

A

bind calcium for plasticity short term

20
Q

In the PDZ domain of RIM what portion of the calcium channel does it interact with to bring calcium channels to active zone?

A

cytosolic tail

21
Q

What does RIM-BP do?

A

links rim to calcium channels

22
Q

How does rim-bp allow for reduncnay in actuve zone?

A

it can also bind the cytosolic tail of calium channels

23
Q

What does munc-13 do?

A

synaptic vesicle priming -primes snare proteins for vesicle fusion
-short term plasticity via priming
-positions synaptic vesicles fusion sites in the active zone
-also has a calcium binding domain and secondary messenger site

24
Q

What does liprin alpha do?

A

meditaes binding of elks/rim to cell adhesion molecules
-helps to establish where and when active zones are formed

25
Q

What is the earliest actuve zone protein?

A

liprin alpha and it also binds to transsyanptic molecules like PTP and LAR

26
Q

What are the two functions of elks?

A

-needed for determining how many synaptic vesicles are at the active zone docked and primed
2. anchors and positions calcium channels
-spans the membrane into the cytosol

27
Q

What is an ideal system to study the active zone and what is used to do this?

A

drosophilia NMJ
-light microscope
-can see T bar with synaptic vesicles and can see that the postsyanptic receptors and active zone are colocalized

28
Q

What forms the T-bar at the active zone?

A

BRP which is the drosophilia elks homolog

29
Q

What microscopy revelaed the T bar is a doughnut?

A

STED microscopy which is a high resolution light microscopy

30
Q

What happened to brp mutants?

A

cant fly so die

31
Q

What is clustered at the center of BRP?

A

calcium channels

32
Q

What is the model of the drosophila active zone?

A

-calcium channels about five center in the middle and and brp anchored one end in plasma membrane to organize calcium channels and one end in cytosol to anchor synaptic vesicles

33
Q

Where are synaptic vesicles patterned in the presynaptic active zone?

A

outside of the highest devsity of actuve zone componenst

34
Q

What is distrubuted throughout the synaptic cleft and where is the highest density of it?

A

proteinacious material and it has the highest density in the outer ring and it has cell adhesion porteins like ephrin LAR and neurexins which allow for transsynaptic alignment

35
Q

What is the patterning of postsyanptic densoty?

A

clusters of receptors found opposute rim and rimbp so active zone

36
Q

What are the three proposed mechanisms for synaptic alignment?

A

1.transsynaptic molecule at pre and post synaptic site
2. calcium channels and post synaptic receptors interact
(glycosylated ec proteins can link calcium channel to glutamate receptor)
3.glutamate itself can cause receptor apposition or retrograde signals from the postsyanptic cell too

37
Q
A

BISC 407 - Cellular and Molecular Neuroscience (23 decks)

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