Neurotransmitter Release - Online Tutor, Practice Problems & Exam Prep

Neurotransmitter release occurs through exocytosis, a process involving SNARE fusion proteins. V-SNAREs, located on vesicles, bind to T-SNAREs on target membranes, overcoming natural repulsion due to negatively charged phospholipids. This binding initiates a four-step process: 1) SNARE binding, 2) hemifusion (partial fusion of outer membranes), 3) creation of a fusion pore, and 4) neurotransmitter release into the extracellular space. Acetylcholine is a key neurotransmitter that triggers muscle contractions, highlighting the importance of this mechanism in cellular communication.

Neurotransmitter Release

In this video, we're going to begin our lesson on neurotransmitter release, and this process occurs via exocytosis. A well-studied example of exocytosis is the release of neurotransmitters in the final step of a neuron signal. Neurotransmitters, as their name implies with the 'neuro' prefix and the 'transmit' root, are just chemical substances that are released by the end of a neuron in order to transmit a signal from one cell to another. A classic example of a neurotransmitter is the molecule called acetylcholine.

Notice that we're showing you the structure of acetylcholine and how acetylcholine gets its name from its structure. There is a choline group and an acetyl group, and that is how acetylcholine gets its name. Acetylcholine is stored in vesicles at the end of a neuron and is released by neurons via the process of exocytosis in order to trigger a muscle contraction. We'll be able to see this in our example image.

Notice at the top here, we have a neuron or a cell of our nervous system. You can see the body of the neuron and the axon of the neuron, which ends in the axon bulbs at the end. This image zooms into the bulb of the axon, representing the end of the axon of the neuron. Acetylcholine is packed into vesicles at the end of the neuron's axon. These vesicles are packed with the acetylcholine molecule described above. Acetylcholine is the neurotransmitter in this case.

Over on the right-hand side of our image, we have a muscle cell and this red line represents the muscle cell's plasma membrane, embedded in which are the acetylcholine receptors. When an action potential makes its way down the axon of the neuron, that action potential is going to trigger calcium to be released into the cell. Calcium, we know, acts as an intracellular signal, and this calcium is ultimately responsible for these vesicles to fuse with the axon's plasma membrane via the process of exocytosis in order to release those acetylcholine neurotransmitters. This is exactly what we're seeing on the right-hand side. Calcium comes into the cell and triggers the exocytosis of these vesicles.

All of these acetylcholine neurotransmitters are being released into the space and those acetylcholine molecules are capable of binding to the acetylcholine receptors. When they do that, they can trigger a muscle contraction within the muscle cell. Exocytosis plays a big role in the triggering of a muscle contraction. This concludes our introduction to neurotransmitters, and as we move forward in our lesson, we're going to talk more details about exactly how neurotransmitter release occurs, and I'll see you guys in our next video.

Neurotransmitter Release

In this video, we're going to introduce SNARE fusion proteins. And so you might recall from some of our previous lesson videos where we first introduced endocytosis and exocytosis, we briefly mentioned that these integral membrane proteins called fusion proteins are important for allowing membranes to fuse together during the process of endocytosis and exocytosis. And so here we are talking about very specific fusion proteins called SNAREs. Now it's also very important to note that vesicles and plasma membranes will actually naturally repel each other. And so the reason for this natural repulsion is because vesicles and plasma membranes are both made of phospholipids and those phospholipids have negatively charged phosphate groups. And so the negatively charged phosphate groups in the vesicles will repel the negatively charged phosphate groups in the plasma membranes and so that is why there is this natural repulsion between the two. And so in order for endocytosis or exocytosis, such as neurotransmitter exocytosis to occur, it is going to need to overcome this natural repulsion between the vesicles and the plasma membranes. And in order to overcome that natural repulsion, it is going to require many different types of proteins. Now moving forward, we're not going to talk about all of the different types of proteins that are involved with overcoming the repulsion. However, we are going to focus in on the integral membrane fusion proteins called SNAREs. And so really there are 2 main types of SNAREs that you should be familiar with and we have them numbered here number 1 and number 2. And so the first SNARE that you should be familiar with is called the V-SNARE. Now as its name implies with the V, the V-SNAREs are going to be found on the intracellular vesicle cytoplasmic surface and so you can see that the V in vesicle is for the V in V-SNARE. And so by intracellular vesicle cytoplasmic surface we are really saying that the V-SNAREs are found on the outside of the intracellular vesicle. Now it's also important to note that sometimes V-SNAREs are referred to as R-SNAREs And the reason for that is because arginine, whose one letter code is R, is a critical amino acid residue in the SNARE protein. And so it's important to know that V-SNAREs and R-SNAREs are the same type of SNARE. And so one way that helps me remember that V-SNAREs and R-SNAREs are the same type of SNARE is that when I think of V-SNARE and R-SNARE I think of V and R or virtual reality. And so notice down below we're showing you this kid with these virtual reality goggles. And so you can see that the virtual reality can remind you of the V-SNARE and the R-SNARE and that the V-SNARE and R-SNARE are the same thing. They're referring to the same thing. Now the second type of SNARE is called the T-SNARE and the T-SNARE is not going to be found on the intracellular vesicle cytoplasmic surface. Instead, the T-SNARE, as its name implies, is going to be found on the target membrane cytoplasmic surface. And so you can think the T in target membrane is for the T and T-SNARE. Now T-SNAREs are also sometimes referred to as Q-SNAREs and the reason for that is because a glutamine residue is critical for the function of the protein and Q is the one letter code for glutamine. And so one way that helps me remember that T-SNAREs and Q-SNAREs are the same type of SNARE is I remember this cartoon character here looking at himself in the mirror and saying, "Hey there cutie looking good." And so that will help you remember hopefully that Q-SNAREs and T-SNAREs are the same type of SNARE. And so here in the middle what we have is, a representation of the end of an axon to help you better understand the difference between the T-SNARE and the Q the T-SNARE and the V-SNARE. And so notice here we have the axon of a neuron here and at the end what we have here is a vesicle and the vesicle is going to perform exocytosis to exit the end of this neuron. And so packed inside of the vesicle is going to be some kind of neurotransmitter, perhaps acetylcholine. And so notice here in green, these green structures that are on the outside of the vesicle, we call these the V-SNAREs. And the V-SNAREs are also known as R-SNAREs and so we could have put either V or R into this blank. And then over here on this side on the target membrane, center on the target membrane cytoplasmic surface what we have is the T-SNARE. And again the T-SNARE is also known as the Q-SNARE. So we could have put T or Q into either of those blanks. And so as we move forward in our course we're going to talk about the specific steps that are required in the process of exocytosis. Where, the V-SNARE will come into contact with the T-SNARE in order to allow the vesicle to fuse with the target membrane and release the contents of the vesicle, release the neurotransmitter. And so again, we'll be able to talk about that step-by-step process as we move forward in our other videos but for now this here concludes our brief lesson on SNARE fusion proteins and I'll see you all in our next video.

V-SNARE proteins deliver _______ to T-SNARE receptor sites.

• A. Ribosomes.
• B. mRNA.
• C. Transport vesicles.
• D. Lysozymes.

True or False: All transport vesicles in the cell have T-SNARE proteins in their membrane.

• A. True.
• B. False.

Neurotransmitter Release

Alright. So now that we've introduced the SNARE fusion proteins, the V-SNARE and the T-SNARE, in this video, we're going to talk about the process of neurotransmitter exocytosis. And so neurotransmitter release via exocytosis occurs in a 4-step process that we have numbered down below in our text. And, of course, the numbers that we have in our text here correspond with the numbers that we have down below in our image. Now over here on the far left, what we have is a little reminder of the SNARE fusion proteins from our last lesson video. And so we know that here, what we have is the V-SNARE on the vesicle membrane. And so this green structure here represents the V-SNARE, and we know that the V-SNARE in some of your textbooks is also referred to as the R-SNARE. And we remember that because VR is like virtual reality. And then, of course, over here in the target membrane, what we have is the T-SNARE. And the T-SNARE is this blue structure that you see here in the target membrane. And again, in some of your textbooks, the T-SNARE is referred to as the Q-SNARE, and we remember that because we think about a cutie. And so, now that we've refreshed our memories on these SNARE fusion proteins, we can talk about the first step of this 4-step process to neurotransmitter exocytosis. And the very first step is SNARE binding. And, of course, during SNARE binding, the V and the T-SNARE are going to bind to each other and induce conformational changes. These conformational changes are going to draw the two membranes closer together. It's going to draw the vesicle membrane closer to the target membrane. Even though they have this natural tendency to repel each other, again, it's the SNARE proteins, fusion proteins, that play a big role in allowing these two membranes to be drawn together. And so down below in our step number 1, which again corresponds with step number 1 up above, you can see that we have V and T-SNARE binding. And so notice that, over here, we have our vesicle and, over here, we have our target membrane, And notice that the V-SNARE and T-SNARE are now bound to each other here, and they are inducing conformational changes in each other that again are drawing the two membranes together. The vesicle membrane and the target membrane are being drawn closer together. So now moving on to the second step, what we have is hemifusion, and this is when changes in the curvature and the lateral tension in both the vesicle membrane and the target membrane are going to induce only the outer sheets of the membranes to fuse with each other. And so it's not the inner sheets, it's only the outer sheets that are fusing. And so it's only like part of the membranes are fusing, partial fusion. And that's exactly what hemifusion is referring to because the prefix hemi means partial. And so hemifusion means partial fusion. And again, that's why it's only inducing the outer sheets of the membrane to fuse, not the inner sheets just yet. And so if we take a look at our step number 2 down below, which again corresponds with step 2 up above, we have hemifusion, again, partial fusion. Here, and notice that it's the outer sheets that are here. And notice that it's the outer sheets that are fusing. So you could see here the outer sheets are fusing and, the inner sheets are still not fusing yet. And so you can see that we have this gap here, where the membranes are beginning to fuse. And so, really, that is it for step number 2. And in step number 3, what we have is the creation of a fusion pore. And so continued changes in curvature and lateral tension, and again, both the vesicle membrane and the target membrane, are ultimately going to fuse both of the membrane sheets, the outer and the inner membrane sheets, so that the vesicle is completely fused to the target membrane. And this is going to create a small opening or a small pore in the, membranes. And so, this is referred to as the fusion pore. And so if we take a look at our step number 3 down below, which, of course, corresponds with step 3 above, we have the generation of the fusion pore. And so notice that now both membranes have been merged. Both sheets of the membranes have been merged, and so it creates this little tiny fusion pore here where neurotransmitters can begin to make their way out to, the extracellular space. And so in step number 4, what we have is release, neurotransmitter release, to be more specific. And so this is when the fusion pore is going to expand and, of course, release neurotransmitters, into the extracellular space, and then the fused membrane is going to take a more relaxed position. And so if we take a look at step number 4, notice that we have release of the neurotransmitters. And so notice that the membranes are now completely fused and it's starting to take more of a relaxed state. The fusion pore has expanded, so now all of the neurotransmitters can be released into the outside of the cell. And so, really, this is the 4-step process for neurotransmitter exocytosis, and we'll be able to get some practice applying some of these concepts as we move forward in our course. So I'll see you guys in our next video.

Neurotransmitter Release Example 1

So here we have an example problem that says that the toxin produced by the bacterium Clostridium tetani, which causes the disease tetanus in humans, is a protease that cleaves and destroys snares. Explain why this would lead to muscle paralysis. Of course, we know from our previous lesson videos that snares are fusion proteins that are critical for the release of neurotransmitters via exocytosis. And so, if these snares are cleaved and destroyed, then that means that the release of neurotransmitters will not be possible. We know that one of the most critical neurotransmitters is Acetylcholine, which when released triggers a muscle contraction in muscle cells.

And so really for this answer what we can do is fill in this statement. And so what you'll notice, it says that destroyed snares will ultimately prevent the release of the neurotransmitter acetylcholine, which normally we know acetylcholine will trigger muscle contractions from our previous lesson videos. And so if we prevent the release of this neurotransmitter acetylcholine, ultimately that is going to interrupt the communication between neurons and muscles, and ultimately that will cause muscle paralysis. And so really this here is the answer to this practice problem. And that concludes this practice or this example, and I'll see you guys in our next video.

The R-SNARE and Q-SNARE proteins are involved in what process?

• A. Formation of vesicles.
• B. Fusion of transport vesicles with the target membrane.
• C. Targeting of transport vesicle to intracellular destinations.
• D. Packaging of neurotransmitters into transport vesicles.
• E. Ligand-gated channel opening.

Here’s what students ask on this topic:

What is the role of SNARE proteins in neurotransmitter release?

SNARE proteins are crucial for the process of neurotransmitter release via exocytosis. They help overcome the natural repulsion between the vesicle and plasma membranes, which are both negatively charged due to their phospholipid content. There are two main types of SNARE proteins: V-SNAREs (found on vesicles) and T-SNAREs (found on target membranes). The binding of V-SNAREs to T-SNAREs initiates a four-step process: 1) SNARE binding, 2) hemifusion (partial fusion of outer membranes), 3) creation of a fusion pore, and 4) neurotransmitter release into the extracellular space. This mechanism ensures that neurotransmitters like acetylcholine are effectively released to trigger responses such as muscle contractions.

How does calcium trigger neurotransmitter release?

Calcium plays a pivotal role in triggering neurotransmitter release. When an action potential reaches the end of a neuron, it causes voltage-gated calcium channels to open, allowing Ca²⁺ ions to enter the neuron. The influx of calcium acts as an intracellular signal that prompts vesicles containing neurotransmitters to move towards and fuse with the plasma membrane. This fusion occurs through the action of SNARE proteins, leading to the exocytosis of neurotransmitters like acetylcholine into the synaptic cleft, where they can bind to receptors on the target cell and elicit a response, such as muscle contraction.

What are the steps involved in neurotransmitter exocytosis?

Neurotransmitter exocytosis involves a four-step process: 1) SNARE binding: V-SNAREs on vesicles bind to T-SNAREs on the target membrane, drawing the membranes closer. 2) Hemifusion: The outer layers of the vesicle and target membranes partially fuse. 3) Creation of a fusion pore: Both the outer and inner layers of the membranes fully fuse, forming a small opening. 4) Neurotransmitter release: The fusion pore expands, allowing neurotransmitters to be released into the extracellular space. This process is essential for the transmission of signals between neurons and target cells, such as muscle cells.

What is acetylcholine and how does it function in neurotransmitter release?

Acetylcholine is a neurotransmitter that plays a key role in transmitting signals from neurons to muscle cells, triggering muscle contractions. It is stored in vesicles at the end of a neuron and released via exocytosis. When an action potential reaches the neuron's axon terminal, it causes calcium ions to enter the cell, prompting vesicles to fuse with the plasma membrane through the action of SNARE proteins. This fusion releases acetylcholine into the synaptic cleft, where it binds to acetylcholine receptors on the muscle cell membrane, initiating a muscle contraction.

What is the significance of hemifusion in the process of neurotransmitter release?

Hemifusion is a critical intermediate step in the process of neurotransmitter release. It involves the partial fusion of the outer layers of the vesicle and target membranes, induced by changes in membrane curvature and lateral tension. This step is essential because it brings the membranes closer together, setting the stage for the complete fusion of both the outer and inner membrane layers. Hemifusion ensures that the vesicle is properly aligned with the target membrane, facilitating the formation of a fusion pore through which neurotransmitters can be released into the extracellular space.