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Activation and inhibition of signal transduction pathways

AP Bio: IST‑3 (EU), IST‑3.G (LO), IST‑3.G.1 (EK), IST‑3.G.2 (EK)

Video transcript

- [Narrator] What we have depicted here is a signal transduction pathway that gets started with the cholera toxin. And we've talked about signal transduction pathways in other videos, but it's really this idea that you would have molecules outside of the cell that would interact with receptors on the surface of the cell that would then create a whole chain reaction of events that would cause that cell to do something. And so what's happening here is, if you were in the unfortunate situation, and this is not something that you would wish on anyone, if they were to have the cholera bacteria in their gut, so let's say that this is the cholera bacteria, that cholera bacteria in your intestines will release the, what we can call the cholera toxin. And here it's depicted in very abstract fashion by a circle on top of a triangle. That's not what it actually looks like. It's a protein complex with various protein subunits. It's just drawn this way so that we can think about this triangle part interacting with this receptor on the epithelial cell. And so what happens is this cholera toxin, it will interact with this ganglioside receptor. You don't have to know the details here, really just the idea of what's going on. And then once it does that, when you see these arrows on these transduction pathways, you could view it as that is going to activate the next step, or sometimes you might say might promote the next step or make it more likely to happen. But what then happens is, is once this thing has interacted, the A part of the subunit goes in, interacts with a G-protein. You don't have to know all the details here, but G-proteins are something that you'll see in a lot of signal transduction pathways. There's not just one G-protein. There's a whole family of proteins called G-proteins. And you can view them as molecular switches. They can get turned on and off based on how they're interacting with other molecules. Their conformation, their shape changes, and so that might activate or deactivate them. But you can see, you can follow these arrows, and you can see what eventually happens. And you don't have to know every detail here. Eventually, it leads to adenylate cyclase, then cyclic AMP, then the protein kinase gets involved. But the end result from this pathway is that you have these ions being released from this epithelial cell. And with that, that causes the water to leave the cell, and that's what causes diarrhea. So the toxin gets your gut cells, gets your intestinal cells to start releasing water, so then you're going to have very, very, very bad diarrhea. So that's the big picture, but now we can think about what might happen in certain situations. So if I were to ask you, let's say this epithelial cell somehow had a mutation, so its ganglioside receptor does not interact well with the B subunit here, with the cholera toxin. What would happen then? Pause this video, and try to think about that. All right, so for whatever reason, this epithelial cell had a ganglioside receptor that was a little bit different, and it couldn't interact as efficiently with the cholera toxin. Well, in that situation, this, this activation would not be happening or at least would not be happening as efficiently. And so someone with that type of a ganglioside receptor, there might be some other negative side effects, but they actually would not get as bad diarrhea from the cholera toxin because this whole signals transduction pathway would not be happening or would not be happening as strong. Now on the other hand, it turns out that there's molecules that can disrupt this signal transduction pathway. So what we have right over here, this is an opioid receptor. And if it gets activated, then it will activate another G-protein. This one is different than the one here, but it's part of that same family. And when you see this type of thing, when you see a line with this flat head instead of an arrow, that means it's inhibiting that process. So for example, this opioid receptor is receptive to a molecule known as enkephalin. Once again, you don't have to know that. But what you should know is that, okay, you have this molecule outside of the cell that can interact with the opioid receptor, which will then activate a G-protein, and what's interesting is that this G-protein is actually an inhibitor of this step right over here. And so if you have cholera and the cholera toxins in your gut, but you also expose those epithelial cells to enkephalin, well, that might make the diarrhea a little bit less bad. Because if this gets disrupted or at least if it gets inhibited, then the rest of this pathway will not happen, or it will not happen quite as strong. So that leaves another question. If there was some mutation in the opioid receptor here, so it wasn't as good at binding to enkephalin, what would be the end result? So if your opioid receptor is somehow not as receptive to enkephalin, well, then enkephalin will not be as effective at being able to stop this signal transduction pathway because the enkephalin will not be able to bind with that opioid receptor. And so this inhibition will not occur, and so you would just have the regular transduction pathway from the cholera toxin occurring, which results in diarrhea. So I'll leave you there. The big thing to appreciate is when you see these pathways, arrows you can view as activation, or they're leading to the next step. And these lines with these flat heads, this is about inhibition. And it's pretty typical to see questions, and, especially if you're a scientist, you might construct these pathways. But you'll also get questions on, hey, if there's a mutation on something that is activating part of the pathway, what will happen? And then the pathway won't happen as much or maybe at all. And if there's a mutation in something that inhibits the pathway, what would happen? Well, if there's a mutation that makes something that would regularly inhibit a pathway less functional, then it won't be able to inhibit the pathway as much, and so the pathway will be less inhibited.
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