hey everyone and this is gonna talk about the ran GTP A's cycle so to begin what is the ran gtp a cycle involved in well it's actually involved in nuclear transport so typically proteins such as transcription factors are transported into the nucleus from the cytosol through nuclear pore complexes and these nuclear pore complexes are composed of around 30 different types of proteins we call nuclei porns now I mentioned the nuclear membrane we also call this a nuclear envelope and it is actually a double membrane so there's actually a double membrane that separates the components of the nucleus from the cytosol so proteins can transport from the cytosol into the nucleus in a couple of different ways and one way is passive diffusion and where they can passively diffuse through nuclear pores and usually proteins of around 60 Cal Dalton's or less can pass through these nuclear pores through passive diffusion now there's been some research showing that it is possible that maybe a little bit bigger proteins can pass through passive diffusion but typically proteins are bigger than 60 Cal Dolan's they have to pass through active transport so proteins going into the nucleus from the cytosol would go in to the nucleus with the help of proteins known as importance in importance bind to their target protein through a nuclear localization signal which is on the target protein and proteins coming out of the nucleus back into the cytosol are actually brought out by the help of proteins known as export ins and export ins bind to their target protein through a nuclear export signal which is located on the target protein and all of these signals the nuclear localization signal in nuclear export signal are simply a sequence of amino acids on the target protein so important in this ran gtp a cycle is this idea of a ran gradient now ran is simply a protein and it can come in a couple of different forms one is ran GDP which is primarily found in the cytosol and the is ran GTP which is primarily found in the nucleus and we'll talk about why that is in the next slide but recognize that in total when we look at all the ran protein in the cell about only five percent is located in the cytosol while the rest of the 95 percent is located in the nucleus so here's our nucleus so we mentioned that proteins entering into the nucleus from the cytosol enter the nucleus through nuclear pore complexes or NPCs now again the nuclear membrane is a double membrane so a lot of proteins like transcription factors which are large have to get into the nucleus through these nuclear pore complexes we also mentioned that proteins less than 60 Cal Dalton's can usually enter the nucleus through nuclear pores by passive diffusion but if the protein is larger than 60 Cal Dalton's it requires some help in the form of active transport with the help of proteins known as importance and they bind to the protein it could be a transcription factor and they bind to these proteins through the amino acid sequence on the protein known as the nuclear localization signal and we mentioned that ran GDPs in the cytosol gdp standing for guanosine diphosphate so ran gdp has two phosphate groups now both of these proteins ran GDP in important alpha or beta with its protein cargo enter into the nucleus through nuclear pore complexes once in the nucleus ran gdp gets acted on by the protein known as RCC one an RCC one is located in the nucleus primarily and it associates with chromatin and what it does is it actually takes an inorganic phosphate and adds it to that ran gdp to form rent GTP which has three phosphate groups now once we have ran GTP we mentioned that most of the ran GTP is located in the nucleus and what it does is it actually binds to important proteins and remember that important is bound to its cargo protein it's bound to its target protein but when ran GTP binds to important protein it actually disrupts the importance ability to bind to its target protein effectively kicking its cargo off of the important protein now we have a dimer ran GTP an important protein bound together now ran GTP can then exit with important out of the nucleus through a nuclear pore complex and back into the cytosol once the ran GTP and important are in the cytosol what happens is that ran GTP gets acted on by a couple of different proteins one is known as ran GAAP or ran GPAs activating protein and the other one is ran binding proteins and these two types of proteins actually increase the GTP a's activity of ran and what that means is that it actually removes one of the fuss phosphate groups off of ran GTP to reform ren gdp once ran GTP has been hydrolyzed to ren gdp it disrupts ren GTP's ability to bind to important and important is effectively kicked off of ren GTP so that was nuclear import but what about nuclear export well nuclear export is pretty much identical to what we saw in the last slide it except for the fact that we use export in proteins and they themselves bind to protein cargo within the nucleus through something else called a nuclear export signal in the export in proteins with their cargo buying to ran GTP and this whole complex of proteins ran GTP export and export as cargo all exit the nucleus through nuclear pore complex into the cytosol now again we've seen that ran GTP gets acted on by Iran GAAP and ran BP to increase his rent GTP A's activity to hydrolyze rent GTP to ram gdp and when rent GTP gets hydrolyzed to ren gdp it again disrupts the binding of exporting to ran GTP effectively kicking off exporting from ran GTP and on top of that the protein cargo gets kicked off of exporting so they all get disrupted from the hydrolyze ation of ran GTP then as we've learned before ran GDP in exporting proteins can enter the nucleus through nuclear pore complexes and the cycle can continue ran gdp can be recycled back into rent GTP in the nucleus via our sec won and the export and protein can be used again to bind to protein cargo in the nucleus which has nuclear export signals anyways guys that was a lesson on the ran GTP a cycle and nuclear transport involving importance and exporters i hope you found this video helpful if you did please like and subscribe for more videos like this one and as always thank you so much for watching and i'll see you next time