Molecular mechanisms of synaptic transmssions Flashcards
The amplitude of evoked resposnses consists of
Multiple quanta
The mini events represent a single synaptic vesicle____________with the presyanotic plasma membrane and releasingn neurotransmitter
Fusion
The quantal content formula indicates __________________________
how many quanta is released
End plate potentials are dependent on ____________________ _________ _______________
External Ca concentrations
What does lower Ca concentration lead to and what does higher Ca concentration lead to?
Lower external Ca concentration leads to smaller end plate potentials or smaller neurotransmitter release
what doesnt change when the external Ca concnetrations are varied?
The amplitude of mini end plate potentials .
Evoked response is dependent on ___________________________________and spontaneous reponse is ____________________ on external Ca
External Ca concentrations, not dependent
What are the different categories of synaptic transmission?
• Synchronous evoked release: the Action potential results in fast synchronous evoked release
Describe synaptic transmission
• An action potential invades a presynaptic terminal
What are the three process that govern neurotransmitter release?
• Localized Ca influx
What are the different neurotransmitter release machinery
Synaptic vesicle fusion machinery
Describe the steps to Ca2+ triggered synaptic fusion
• Synaptic vesicles localized near the presynaptic active zone
What are the 4 mechanisms that are critical for synchronous release
- a nerve terminal needs to generate and maintain a pool of redly releasable vesicles that can quickly be exocytosed upon Ca entry.
List some Presyanptic proteins
• SNARES (synaptobrevin, SNAP 25, syntaxin)
What are SNARE motifs and a transmembrane domain?
SNARE motifs allow for proteins to interact with each other.
Why is synaptobrevin a syanaptic vesicle protein rather than a plasma membrane protein?
Since synaptobrevin has the transmembrane domain on its membrane synaptobrevin is able to attach itself to the synaptic vesicle
Why are SNAP 25 and syntaxin found on the plasma membrane
Because their transmembrane is on the presynaptic plasma membrane.
What do Botulinum toxins do?
Cleave SNARE proteins, and prevent them from forming a SNARE complex (SNARES are important for neurotransmitter release)
What botulinum toxins are synaptobrevin, SNAP 25 and syntaxin cleaves by?
Synaptobrevin is cleaved by: BoNT/F, D, B, and G
what is the result of knocking out synaptobrevin 2 in mice?
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.
what is the result of knocking out SNAP 25 in mice?
There is a severe reduction in evoked neurotransmission release than spontaneous release. Spontaneous neurotransmission is still present.
what is the result of knocking out syntaxin in mice?
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.
What SNARE proteins form the SNARE complex
Synaptobrevin, Syntaxin and SNAP 25
What proteins are critical for dissassebling the SNARE complex?
NSF and a-SNAP
What are SNARE chaperones and what is their purpose?
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
What will happen if you remove synuclein ?
We will be inhibiting the SNARE complex resulting in less SNARE complex assembly
Describe the Munc-18 protein
• Munc-18 binds to syntaxin which is a SNARE protein found on the plasma membrane
How does Mun-18 bind to the closed and open conformations of syntaxin 1
• Munc-18 binds to syntaxin-1 when it was in the closed conformation where it is not able to bind to other SNARE proteins
Membrane fusion requires two conformational transitions
- Switch from closed to open Syntaxin 1A, both which are complexed to Munc-18
Describe the Domain and structure of Ca binidng on Synaptotagmin 1 which was found to be molecule x
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.
Does Ca binding to synaptotagmin affinity affect neurotransmissiom?
• 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)
Do all synaptotagmins function the same?
Synaptotagmin 1 2 and 9 can act as Ca sensors for evoked synchronous neurotransmitter release
reseach syggests that ________________________________is a Ca sensor for asynchronous neurotransmitter release
synaptotagmin 7
Describe all the synaptotagmins and what where they are important?
• For fast synchronous neurotransmission synaptotagmin 1,2 and 9 are Ca sensors
Describe Doc2b and why it is important
• 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.
Describe Complexin and why it is important
• Binds to Snare protein/complexes
How does complexin work as a Clamp and an activator?
• For complexin to act as an activator for evoked neurotransmitter it needs to bind to SNARE proteins
describe complexins shape
• Complexin has a helix that allows it to bind to SNARE proteins
what does complexin prevent while acting as a clamp
excessive spontaneous neurotransmission
Ca triggered neurotransmitter release
• Need the docking step and partial assembly of snare complex
