Molecular mechanisms of synaptic transmssions

Question 1

The amplitude of evoked resposnses consists of

Answer 1

Multiple quanta

Question 2

The mini events represent a single synaptic vesicle____________with the presyanotic plasma membrane and releasingn neurotransmitter

Answer 2

Fusion

Question 3

The quantal content formula indicates __________________________

Answer 3

how many quanta is released

Question 4

End plate potentials are dependent on ____________________ _________ _______________

Answer 4

External Ca concentrations

Question 5

What does lower Ca concentration lead to and what does higher Ca concentration lead to?

Answer 5

Lower external Ca concentration leads to smaller end plate potentials or smaller neurotransmitter release

Question 6

what doesnt change when the external Ca concnetrations are varied?

Answer 6

The amplitude of mini end plate potentials .

Question 7

Evoked response is dependent on ___________________________________and spontaneous reponse is ____________________ on external Ca

Answer 7

External Ca concentrations, not dependent

Question 8

What are the different categories of synaptic transmission?

Answer 8

• Synchronous evoked release: the Action potential results in fast synchronous evoked release

Question 9

Describe synaptic transmission

Answer 9

• An action potential invades a presynaptic terminal

Question 10

What are the three process that govern neurotransmitter release?

Answer 10

• Localized Ca influx

Question 11

What are the different neurotransmitter release machinery

Answer 11

Synaptic vesicle fusion machinery

Question 12

Describe the steps to Ca2+ triggered synaptic fusion

Answer 12

• Synaptic vesicles localized near the presynaptic active zone

Question 13

What are the 4 mechanisms that are critical for synchronous release

Answer 13

1. a nerve terminal needs to generate and maintain a pool of redly releasable vesicles that can quickly be exocytosed upon Ca entry.

Question 14

List some Presyanptic proteins

Answer 14

• SNARES (synaptobrevin, SNAP 25, syntaxin)

Question 15

What are SNARE motifs and a transmembrane domain?

Answer 15

SNARE motifs allow for proteins to interact with each other.

Question 16

Why is synaptobrevin a syanaptic vesicle protein rather than a plasma membrane protein?

Answer 16

Since synaptobrevin has the transmembrane domain on its membrane synaptobrevin is able to attach itself to the synaptic vesicle

Question 17

Why are SNAP 25 and syntaxin found on the plasma membrane

Answer 17

Because their transmembrane is on the presynaptic plasma membrane.

Question 18

What do Botulinum toxins do?

Answer 18

Cleave SNARE proteins, and prevent them from forming a SNARE complex (SNARES are important for neurotransmitter release)

Question 19

What botulinum toxins are synaptobrevin, SNAP 25 and syntaxin cleaves by?

Answer 19

Synaptobrevin is cleaved by: BoNT/F, D, B, and G

Question 20

what is the result of knocking out synaptobrevin 2 in mice?

Answer 20

Removing synaptobrevin 2 results in a severe decrease in neurotransmission because it leads to less frequency of synaptic vesicles fusing. We also see a reduction in evoked and spontaneous neurotransmission but the effect is worse for evoked transmission. Spontaneous neurotransmission is still present.

Question 21

what is the result of knocking out SNAP 25 in mice?

Answer 21

There is a severe reduction in evoked neurotransmission release than spontaneous release. Spontaneous neurotransmission is still present.

Question 22

what is the result of knocking out syntaxin in mice?

Answer 22

There is a severe reduction in evoked neurotransmitter release. Spontaneous neurotransmission is still present but it is less than what is present in synaptobrevin 2 and SNAP 25.

Question 23

What SNARE proteins form the SNARE complex

Answer 23

Synaptobrevin, Syntaxin and SNAP 25

Question 24

What proteins are critical for dissassebling the SNARE complex?

Answer 24

NSF and a-SNAP

Question 25

What are SNARE chaperones and what is their purpose?

Answer 25

CSP and synucleins can bind to various SNARE proteins and act as SNARE chaperones and are important for folding and unfolding these proteins. And they can also help prevent neurodegeneration

Question 26

What will happen if you remove synuclein ?

Answer 26

We will be inhibiting the SNARE complex resulting in less SNARE complex assembly

Question 27

Describe the Munc-18 protein

Answer 27

• Munc-18 binds to syntaxin which is a SNARE protein found on the plasma membrane

Question 28

How does Mun-18 bind to the closed and open conformations of syntaxin 1

Answer 28

• Munc-18 binds to syntaxin-1 when it was in the closed conformation where it is not able to bind to other SNARE proteins

Question 29

Membrane fusion requires two conformational transitions

Answer 29

1. Switch from closed to open Syntaxin 1A, both which are complexed to Munc-18

Question 30

Describe the Domain and structure of Ca binidng on Synaptotagmin 1 which was found to be molecule x

Answer 30

We can have this transmembrane domain on synaptotagmin 1 which allows it to be on this synaptic vesicle membrane and we have 2 Ca binding domains called C2A and C2B and these two domains can bind to 5 Ca ion.

Question 31

Does Ca binding to synaptotagmin affinity affect neurotransmissiom?

Answer 31

• Looking at one mutant that had a higher affinity for Ca by mutating the binding domains of synaptotagmin (these have a larger amount of evoked neurotransmission)

Question 32

Do all synaptotagmins function the same?

Answer 32

Synaptotagmin 1 2 and 9 can act as Ca sensors for evoked synchronous neurotransmitter release

Question 33

reseach syggests that ________________________________is a Ca sensor for asynchronous neurotransmitter release

Answer 33

synaptotagmin 7

Question 34

Describe all the synaptotagmins and what where they are important?

Answer 34

• For fast synchronous neurotransmission synaptotagmin 1,2 and 9 are Ca sensors

Question 35

Describe Doc2b and why it is important

Answer 35

• Dco2b is another Ca binding protein; knocking it has no effect on evoked neurotransmission. But if we look at spontaneous neurotransmission we see that the frequency of these events is severely reduced in the absence of Doc2b.

Question 36

Describe Complexin and why it is important

Answer 36

• Binds to Snare protein/complexes

Question 37

How does complexin work as a Clamp and an activator?

Answer 37

• For complexin to act as an activator for evoked neurotransmitter it needs to bind to SNARE proteins

Question 38

describe complexins shape

Answer 38

• Complexin has a helix that allows it to bind to SNARE proteins

Question 39

what does complexin prevent while acting as a clamp

Answer 39

excessive spontaneous neurotransmission

Question 40

Ca triggered neurotransmitter release

Answer 40

• Need the docking step and partial assembly of snare complex