Embedded into the nuclear envelope are nuclear pore complexes (NPC) that transport materials in and out of the nucleus both ways. The material must has a signal to be either transported in and or out of the nucleus. NLS - to transport in NES - To transport out NRS- to retain inside the nucleus CRS- To stay inside in cytoplasm.
First anything under about 40kD can move inside the nucleus and out with ease as they just diffuse down there concentration gradient. Larger molecules must have a signal meaning about 40kD. They either have 1 listed above or both NLS and NES, which means they are a shuttle protein which i will talk about later when I go into RAN.
NLS - Nuclear localization signal for import into the nucleus. Its a permanent signal, and not cleaved bedore or after the translocation to the nucleus. Positive charges also play an important role in importing the SV40 gene (first to be experimentally tested) has a stretch of positive amino acid sequences which work as NLS. But if you change the sequence of this amino acid stretch you will weaken or block the function all together of the NLS. There can be monopartite signals like NLS (one stretch) or 2 which is called a Bipartite cluster (which needs a spacer between the 2 signals)
So lets start.
The NLS receptor and the NLS-containing cargo bind with importin A and inportin B. No energy required
They dock (this can be performed at low temp 4* and doesnt require energy)
NLS receptor and complex translocate across the NPC
Then GTP-Ran binds the B-subunit and it falls off. What is left is the a-subunit and the protein and the NLS
The receptor a and the protein complex break apart and the a-subunit with binds to RAN-GTP and is carried back to the cytoplasmic side.
This is how we get directionality with RAN. GDP cytoplasm GTP in the nuclease because its a GTPase.
There are several accessory proteins working as well. RCC1 which is a GEF - nucleotide exchange factor. It transfers GDP to GTP. It is located in the nucleus- think about this it makes sense - GTP in the nucleus is what the cell needs.
The GTP to GDP are called RanGAP and RanBP1/2
The nuclear export have hydrophobic amino acids like the (HIV rev protein) and this acts to export but RAN is still required.
Once they transporter is back into the cytoplasm it gets ran GTP to ran GDP by RanGAP or RanBP1/2
How is this whole mechanism regulated?
Well chaperones work to mask the NLS. So regulation can be controlled that way.
Nuclear transport
DLW Bachelor of Science,
Anatomy and Cell Biology 2012 McGill University
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The control center of a cell is the nucleus. It contains the cell's genetic material in the form of DNA, which regulates cell activities such as growth, metabolism, and reproduction.
Nuc stands for nucleus which is the center of the cell