Editing Nuclear pore complex (section)

=== Import of proteins ===
{{Main|Nuclear localization signal}}
Nuclear proteins are synthesized in the cytoplasm and need to be imported through the NPCs into the nucleus. Import can be directed by various signals, of which nuclear localization signal (NLS) are best characterized.<ref>{{cite journal |last1=Görlich |first1=Dirk |title=Nuclear protein import |journal=Current Opinion in Cell Biology |date=June 1997 |volume=9 |issue=3 |pages=412–419 |doi=10.1016/s0955-0674(97)80015-4 |pmid=9159081 |hdl=11858/00-001M-0000-002D-1CC5-E |hdl-access=free }}</ref> Several NLS sequences are known, generally containing a conserved sequence with basic residues such as PKKKRKV. Any material with an NLS will be taken up by importins to the nucleus.{{citation needed|date=May 2024}}

Importation begins with Importin-α binding to the NLS sequence of cargo proteins, forming a complex. Importin-β then attaches to Importin-α, facilitating transport towards the NPC.{{citation needed|date=May 2024}}

As the complex reaches the NPC, it diffuses through the pore without the need for additional energy. Upon entry into nucleus, RanGTP binds to Importin-β and displaces it from the complex. Then the ''[[cellular apoptosis susceptibility protein]]'' (CAS), an exportin which in the nucleus is bound to RanGTP, displaces Importin-α from the cargo. The NLS-protein is thus free in the nucleoplasm. The Importinβ-RanGTP and Importinα-CAS-RanGTP complex diffuses back to the cytoplasm where [[Guanosine triphosphate|GTPs]] are hydrolyzed to GDP leading to the release of Importinβ and Importinα which become available for a new NLS-protein import round.{{citation needed|date=May 2024}}

While translocation through the NPC is not energy-dependent, the overall import cycle needs the hydrolysis of two GTPs molecules, making it an active transport process. The import cycle is powered by the nucleo-cytoplasmic RanGTP gradient. This gradient arises from the exclusive nuclear localization of RanGEFs, proteins that exchange GDP to GTP on Ran molecules. Thus, there is an elevated RanGTP concentration in the nucleus compared to the cytoplasm.{{citation needed|date=May 2024}}