ER Processing and Transport

Hi in this video we're gonna be talking about er processing and transport. So this first video is going to focus specifically on two types of er transport. And when we talk about er transport. What we're talking about is how proteins are getting into the E. R. So the first type is co translational import and that's going to be the process of import. We're importing proteins into the er as they're being translated co translational. So how this happens is that an M. RNA is gonna contain what's known as an E. R. Signal sequence. Now the M. RNA that has that signal sequence is going to just be directed to the er and when it's there it's going to recruit ribosomes and other things that it needs in order to be able to translate and also enter into the er So how it does this is the er signal sequence is recognized by what's known as the srp. So the signal recognition particle and that's gonna bind to the signal sequence. Then that particle recognizes its own receptor. The signal recognition particle receptor that's located on the er and it binds to the srp which remember is bound to the er signal sequence. So you have this complex of three things the M. RNA. With the signal sequence the particle that recognizes that signal sequence and the receptor that recognizes that particle. Then when all three of those are bound together and they're bound to all the right things. They come in contact with the poor and the er called a trans Logan and that is going to bind to all of these things and trans locate that protein into the r. As it's being translated to do that it needs energy of course everything needs energy. So it uses that energy from GTP hydraulic sis. So remember that's going to be turning G. T. P into G. D. P. And then once that protein enters into the er has been translated is now in the er it no longer needs that signal because it's already there. So this protein called a signal peptide days comes in and cleaves off that er signal. So what this looks like is if we have a approaching here it has a signal sequence or er signal sequence. Oh the little delay then it recruits the signal recognition particle. You can see that binds here. This eventually binds the receptor and this results in translocation of the protein across to the er lumen. So that's the first type. Now let's go over the second and that's going to be post translational import. This is going to be the process of importing proteins into the er after or post translation. Now in order for this to happen the protein still has to be unraveled. You can't get this huge folded protein across these little pores. So what happens is that they're the protein here is going to be unraveled into a single string and then um it gets transported across into the er and then once it's here it needs to be re folded. So the protein responsible for that is is called hip. And that helps pull the protein across and it interacts with it and helps it refold once it's across. So now that you have proteins in the er you want to keep them there because they have some kind of function. And so the signal is that does that is called an er retention signal which makes complete sense, retains this protein in the E. R. It's located on the c terminus. Um And it's what keeps proteins there. So those are the two types of ways of getting protein into the er. So with that let's not turn the page.

Okay, so in this video we're going to talk about how proteins are inserted into membrane. So we know that there's a lot of trans membrane proteins, they exist all throughout the plasma membrane and and other organelles. And so how do those proteins actually get into the membrane? They're not made in the membrane right there may elsewhere but they have to be inserted. So we're gonna talk about how that insertion process happens. And the first way we're going to talk about it is through single past trans membrane proteins and single pass. Just means that they enter into the membrane once. So they have one insertion. And so you have you have this kind of a long string of a protein and only at one point of that protein is it inserted into the membrane. And so it looks kind of like this one down here, which I'm going to go over in just a second. But how do these proteins actually get into the membrane? Well, there's actually specific sequences that allow them to insert. And there's two sequences you need to know about the start sequence. And the stock sequence. Obviously the start sequence is going to start that initiation process. And getting it into the membrane and the stop sequence is going to stop it. And so pretty much how the start sequence works is it's a sequence on the protein. And what happens is um it comes to the membrane that it wants to insert in and it interacts with a trans low con which is just another type of protein that will allow it to insert into the membrane. And so it starts it it starts inserting right there. But then when it encounters a stop sequence it says okay I'm not doing this anymore and it stops the protein is stuck there, it wherever it is. Now what happens is you see still have the start sequence which is actually stuck in the membrane and that actually gets chopped off by another protein. And I'll show you an example of how this happens. And pretty much these sequences can be located anywhere on the protein. They don't have to be located on the inter ministry is kind of the first part of the protein be located in the middle. It could be located in the end just wherever that protein is going to insert in the membrane, it doesn't have to be in the middle but it just has to be somewhere. Let me show an example of this. So this is a single pass protein getting into the membrane. You can see here we have our like protein line, we have a start sequence here in red and we have a stop sequence. And what happens is that the start sequence gets inserted into the membrane and this is trans con remember and it says, hey we're going to start we're going to insert the protein and the protein is fed through just little by little see until it reaches the stop sequence where it stops this process process stops. And so now we have this protein that's actually integrated into the membrane twice through both. The start sequence here in red and the stop sequence. But we don't want that because remember this is a single pass protein. So a protein called a signal peptide test comes in and it chops this off, right? And now we have a single past protein which is inserted into the membrane. It disassociates from the trans low con. Let's see, it's not worth it anymore. And the start sequence is just sort of recycled in the membrane. So here's how we get a single pass trans membrane protein, the start sequence in our first until it sort of feeds it through slowly until it reaches the stop sequence. Start sequence is cleaned off, separates from the trans lo con. And we have our single pass protein. Now that's for single passes. But not all membrane proteins are single past proteins. Remember some of them are multi pass proteins, meaning that they are sort of passing through the membrane multiple different times. And so they have more than one insertion, more than one insertion. And so in order to do this, what happens is that they don't just contain one start and one stop sequence. They contain multiple start and stop transfer sequences. And so pretty much the start and stop transfer sequences and multi pass trans membrane protein don't actually look different. It's not that one's red and one's orange like I showed you before they actually look the same and they have the same sequence essentially. But it's just the order of them that determines whether their start or whether they're stopped. So the start sequence is the one that the trans Loken encounters first. The stop sequence is the one that encounters second. Then if it encounters a third one, that'll be a start. Then if it encounters 1/4 1, that'll be a stop. And so it keeps just going back, it starts with start, go, start, stop, start, stop until it just runs out of these transfer sequences. And so what does this actually look like here is an example, I can disappear. You can see it here's an example that looks very similar but in this case this will be a multi pass trans membrane protein. So we have a start sequence and a stop sequence exactly like before it enters exactly like before where the start sequence is here and then it encounters a stop sequence. Um and then because this is a multi pass with only to pass, it's going to disassociate from the trans low con and you'll have two passes through the membrane this first one and the second. Now, if the protein was longer, let's say it goes out here, right, and we had potentially another start sequence. Oh, that's not blue. So if we had another start sequence here and another stop sequence here, what would happen is that this sequence would again go back into the membrane and this one would stop it. And it would end up as a four multi pass trans membrane protein instead of a two. So the number of times that this protein enters and exits the membrane determines how many multi pass is it. Is it too? Is in this case, is that four is in this case is at seven. Just depends on how many starts and stops sequences there are. And so it pretty much can go on forever. A really common number is seven. Um so we'll see that a lot with membrane proteins that insert into the membrane seven different times. So if it was the case of a seven multi pass trans membrane protein, what would they have? They would have a start, right at the first start, they'd have a stop, they have a start, they have a stop, they have a start, we have to stop and then a start and it would end here so that it passed through the membrane 1234567 times. So that is how proteins either single path or multi pass insert into the membrane. So with that let's move on

okay in this video, I'm gonna be talking about different er modifications that happen for proteins. So proteins they have to go out into the cell do a lot of things um and so before they want to head out in the cell they need to make sure that they look right. So they need to have all the different modifications their hair and their makeup dine before they can head out and to sell to do things. So the er is a major source of this modification kind of thinking is like a hair salon or something fixing up these proteins so that they can get ready to go out and do their functions. So the first type of modification that happens is going to be glad constellation and this is gonna be the addition of a sugar in case you don't remember why glide constellation is and like oscillation occurs in the er first. So how this happens is there's this precursor molecule, Dollar call and that gets added onto any protein that's going to be glycol insulated. So it's the the same molecule and anything that needs, it is going to be it's going to be added on first. So for all the women out there used to or know anything about makeup for men to be choosy Dollar calls, kind of like the foundation. So that gets added on first before anything else happens. And then um once uh that precursors added on it can be modified, you know, you can add things to it, you can take things away from it but that's gonna be the foundation that goes on Any protein that needs like oscillation and so um this is super important. Super important for proteins because um these sugars that are added on are the foundations that are added on our tags. They mark this protein for proper folding. And it's been determined actually that the chaperone proteins that are responsible for protein folding actually bind the protein through binding um different sugars that have been added on through like oscillation. So the chaperones bind the sugars and that helps them bold everything into the correct place. So black oscillations. Super important. Then you have this G. P. I. Anchor. I'm not even gonna attempt to say that I suggest you don't either. You'll always see it as G. P. I. Um And so this is an anchor that's added to proteins that um are destined for the plasma membrane. So why is this anchor added? Well this anchor is added because if you add if you add an anchor to a protein that anchors it to the plasma membrane. But then at any other point you want to just kind of cut it off. Just cut it off and release it into the night. And so G. P. I. Anchors are added to proteins that are generally going to be released into the cell or released into the extra cellular environment. So G. P. I. Anchors is another thing that happens in er it's super super important. So this is an example of my consolation. So this is what I said about you know your foundation. Um so you have all these different Allah go sacrifice that can be added onto proteins. But it all starts with this molecule and this molecule is added on and then it's further modified to whatever it wants to be in different components or different cellular organelles but it starts out all the same way as this this molecule. Now another thing that happens is this protein called protein di sulfide isOM arrays helps with the formation of di sulfide bonds. So di sulfide bonds are you know these really strong um bonds that help keep the protein together and just sort of help keep it shaped and bond in the way that it should be. So protein di sulfide I summarize helps to do that and then you have the unfolded protein response. So you can kind of imagine this is like your friend when you go out at night because it's going to detect the misfolded protein. So it's going to tell those proteins and say hey you really don't look good enough to go out tonight. So um what we're gonna do is we're just actually going to redo this whole thing. So the unfolded protein response has these proteins called Iraq proteins. It's kind of like your friend. And so the ride proteins they come in they say oh dear goodness you do not look right so these are proteins that are misfolded. They say no you can't go out like that. So what they do is they transport them to the side of salt and eventually degrade them. But let's hope your friends don't degrade you and you're not looking that great and want to go out. So um so this is what happens with the unfolded protein response, you have this protein transported er and then normally it looks good, it looks like it's folded well and it's ready to go out into the world, but sometimes it's something happens and it aggregates or misfolds or it doesn't look very good. So you got a new haircut and it's really not good for you. Um and so the unfolded protein response and these sherrod proteins come in and they say, nope, you're not going to go out. So what they do is they transport these things into the side us all and degrade them. And so you can kind of think that as like your friend pushing you into your closet and telling you to find a new outfit. So that's the unfolded protein response. So with that let's now move on