Mechanism of Nuclear Transport | RAN GTPase Cycle

The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes (NPCs). Although small molecules can enter the nucleus without regulation,[1] macromolecules such as RNA and proteins require association with transport factors like karyopherins called importins to enter the nucleus and exportins to exit.

Protein that must be imported to the nucleus from the cytoplasm carry nuclear localization signals (NLS) that are bound by importins. A NLS is a sequence of amino acids that acts as a tag. They are diverse in their composition and most commonly hydrophilic, although hydrophobic sequences have also been documented.[1] Proteins, transfer RNA, and assembled ribosomal subunits are exported from the nucleus due to association with exportins, which bind signaling sequences called nuclear export signals (NES). The ability of both importins and exportins to transport their cargo is regulated by the small Ras related GTPase, Ran.

GTPases are enzymes that bind to a molecule called guanosine triphosphate (GTP) which they then hydrolyze to create guanosine diphosphate (GDP) and release energy. Ran is in a different conformation depending on whether it is bound to GTP or GDP. In its GDP bound state, Ran is capable of binding karyopherins (importins and exportins). Importins release cargo upon binding to RanGTP, while exportins must bind RanGTP to form a ternary complex with their export cargo. The dominant nucleotide binding state of Ran depends on whether it is located in the nucleus (RanGTP) or the cytoplasm (RanGDP).

[Sifou]

Thank you for the explaination, however you talked about NLC is it another name of the NLS or is it just a mistake ? (excuse for my english I'm french don t sue me)

[ronakchetani]

Even unacademy fails to explain this ❤ Saviour tysm 💥💥💥

[ifeanyichukwueke]

You did an excellent job here! I really enjoyed watching the video! But I want to quickly point out something: Ran-GDP do not bind to the importins. This is what provides for the directionality of the transport. Hydrolysis of the Ran-GTP by GAP releases the phosphate and Ran-GDP in the cytosol. The free importin which had already been docked to the FG-repeats of the NPC is then free to bind to the NLS of the cargo. Transportation occurs. Generally, I will STRONGLY recommend your video!

[tugbasehitogullar]

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[alissakivan]

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[rew_]

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[adnanshah]

You explained it better than my professor lol. Thanks.

[anwyn]

bless your channel. saving my life right now

[anushkasupakar]

Hi,
I just want to clear a few doubts, first about the process of import, that the Importin-cargo complex doesn't require Ran-GDP for their import through NPC. The complex is self-sufficient to import through the NPC, wherein in the nucleoplasm, it binds to RAN-GTP( which has been formed from the nucleoplasm localized RAN-GDP), which causes disassociation of Importin and the cargo. After that the RAN-GTP-Importin complex is exported out through the NPC, wherein the cytoplasm, the GAP hydrolyzes the GTP TO GDP, and the RAN-GDP is recycled back to nucleoplasm through a facilitator protein called NUTF2.
The process of export is same as starting from RAN-GTP binding to exportin, which is transported to the cytoplasm where the GAP protein hydrolyzes the GTP to GDP, and the RAN-GDP is as usual transported back to nucleoplasm through NUTF2.
Please clarify! thank you. :)

[taylormaynard]

Such a simplified explanation makes it much easier to understand, thank you

[Wordboost]

Mere words could not express how much ur lectures are meant for us... 👏

[marcelabuia]

I’ve got a cellular biology exam tomorrow and this video just saved me! Thanks, extremely well explained! 🙌🏼

[hayattkisakuslarucuyo]

Thank you soooo muchhhh
For a few days later I have medical biology exam and I couldn’t understand this part so with your help I could 👌🏻👌🏻👌🏻 now it is clearer than before

[brainfreeze]

Your diagrams are cool and it helps me a lot! Great straightforward explanation and it's just what I needed. I wish you were my molecular professor. Sincerely,
a sleep deprived college student.

[Iceletters]

minute 2:02 when drawing the nuclear membrane...nuclear membrane is a DOUBLE membrane (the inner and the outer) so there are TWO lipid bilayer both of them are crossed by this nuclear pore complex

[PhoenixArchangelAQW]

I don't really comment much, but logged in to say excellent video my man, much appreciated :)

[Somani-ik]

This is actually the best video, I understand everything which I wasnot Been able to understand in lecture

[LumTheAlien]

You explained this 1000 times better then my professor…

[abigailbui]

I love your videos. Your handdrawn diagrams are awesome and I love to copy them. Thank you!

[ScoopTV]

This is an amazing video Hussain. I am very thankful for you!