Editing Nuclear pore complex (section)

== Assembly of the NPC ==
[[File:Blausen 0212 CellNucleus.png|thumb|Cell nucleus containing nuclear pores.]]
Since the NPC regulates genome access, its presence in significant quantities during [[cell cycle]] stages characterized by high transcription rates is crucial. For example, cycling mammalian and yeast cells double the amount of NPC in the nucleus between the G1 and G2 phase. Similarly, oocytes accumulate abundant NPCs in anticipation of the rapid mitotic activity during early development. Moreover, [[Interphase|interphase cells]] must maintain NPC generation to sustain consistent NPC levels, as some may incur damage. Furthermore, certain cells can even increase the NPC numbers due to increased transcriptional demand.<ref name="linkinghub.elsevier.com">{{cite journal | vauthors = Rabut G, Lénárt P, Ellenberg J | title = Dynamics of nuclear pore complex organization through the cell cycle | journal = Current Opinion in Cell Biology | volume = 16 | issue = 3 | pages = 314–321 | date = June 2004 | pmid = 15145357 | doi = 10.1016/j.ceb.2004.04.001 }}</ref>

===Theories of assembly===
There are several theories as to how NPCs are assembled. As the immunodepletion of certain protein complexes, such as the Nup 107–160 complex, leads to the formation of poreless nuclei, it seems likely that the Nup complexes are involved in fusing the outer membrane of the nuclear envelope with the inner and not that the fusing of the membrane begins the formation of the pore.{{citation needed|date=May 2024}} There are several ways that this could lead to the formation of the full NPC.
* One possibility is that as a protein complex it binds to the [[chromatin]]. It is then inserted into the double membrane close to the chromatin. This, in turn, leads to the fusing of that membrane. Around this protein complex others eventually bind forming the NPC. This method is possible during every phase of mitosis as the double membrane is present around the chromatin before the membrane fusion proteins complex can insert. Post mitotic cells could form a membrane first with pores being inserted into after formation.{{citation needed|date=May 2024}}
* Another model for the formation of the NPC is the production of a prepore as a start as opposed to a single protein complex. This prepore would form when several Nup complexes come together and bind to the chromatin. This would have the double membrane form around it in during mitotic reassembly. Possible prepore structures have been observed on [[chromatin]] before [[nuclear envelope]] (NE) formation using electron microscopy.<ref>{{cite journal | vauthors = Sheehan MA, Mills AD, Sleeman AM, Laskey RA, Blow JJ | title = Steps in the assembly of replication-competent nuclei in a cell-free system from Xenopus eggs | journal = The Journal of Cell Biology | volume = 106 | issue = 1 | pages = 1–12 | date = January 1988 | pmid = 3339085 | pmc = 2114961 | doi = 10.1083/jcb.106.1.1 }}</ref> During the interphase of the cell cycle the formation of the prepore would happen within the nucleus, each component being transported in through existing NPCs. These Nups would bind to an importin, once formed, preventing the assembly of a prepore in the cytoplasm. Once transported into the nucleus Ran GTP would bind to the importin and cause it to release the cargo. This Nup would be free to form a prepore. The binding of [[importin]]s has at least been shown to bring Nup 107 and the Nup 153 nucleoporins into the nucleus.<ref name="linkinghub.elsevier.com"/> NPC assembly is a very rapid process yet defined intermediate states occur which leads to the idea that this assembly occurs in a stepwise fashion.<ref>{{cite journal |last1=Kiseleva |first1=Elena |last2=Rutherford |first2=Sandra |last3=Cotter |first3=Laura M. |last4=Allen |first4=Terence D. |last5=Goldberg |first5=Martin W. |title=Steps of nuclear pore complex disassembly and reassembly during mitosis in early Drosophila embryos |journal=Journal of Cell Science |date=15 October 2001 |volume=114 |issue=20 |pages=3607–3618 |doi=10.1242/jcs.114.20.3607 |pmid=11707513 }}</ref>

===Disassembly===
During mitosis the NPC appears to disassemble in stages, except in lower eukaryotes like yeast, where NPC disassembly does not happen during mitosis.<ref>{{cite journal |last1=Hampoelz |first1=Bernhard |last2=Andres-Pons |first2=Amparo |last3=Kastritis |first3=Panagiotis |last4=Beck |first4=Martin |title=Structure and Assembly of the Nuclear Pore Complex |journal=Annual Review of Biophysics |date=6 May 2019 |volume=48 |issue=1 |pages=515–536 |doi=10.1146/annurev-biophys-052118-115308 |pmid=30943044 }}</ref> Peripheral [[nucleoporin]]s, such as the Nup153 Nup98 and Nup214, disassociate from the NPC. The rest, which can be considered a [[scaffold protein]]s remain stable, as cylindrical ring complexes within the nuclear envelope. This disassembly of the NPC peripheral groups is largely thought to be phosphate driven, as several of these nucleoporins are phosphorylated during the stages of mitosis. However, the enzyme involved in the phosphorylation is unknown in vivo. In metazoans (which undergo open mitosis) the NE degrades quickly after the loss of the peripheral Nups. The reason for this may be due to the change in the NPC's architecture. This change may make the NPC more permeable to enzymes involved in the degradation of the NE such as cytoplasmic tubulin, as well as allowing the entry of key mitotic regulator proteins. In organisms that undergo a semi-open mitosis such as the filamentous fungus ''[[Aspergillus nidulans]]'', 14 out of the 30 nucleoporins disassemble from the core scaffold structure, driven by the activation of the NIMA and Cdk1 kinases that phosphorylate nucleoporins and open nuclear pores<ref>{{cite journal | vauthors = Markossian S, Suresh S, Osmani AH, Osmani SA | title = Nup2 requires a highly divergent partner, NupA, to fulfill functions at nuclear pore complexes and the mitotic chromatin region | journal = Molecular Biology of the Cell | volume = 26 | issue = 4 | pages = 605–621 | date = February 2015 | pmid = 25540430 | pmc = 4325833 | doi = 10.1091/mbc.E14-09-1359 }}</ref><ref>{{cite journal | vauthors = De Souza CP, Osmani AH, Hashmi SB, Osmani SA | title = Partial nuclear pore complex disassembly during closed mitosis in Aspergillus nidulans | journal = Current Biology | volume = 14 | issue = 22 | pages = 1973–1984 | date = November 2004 | pmid = 15556859 | doi = 10.1016/j.cub.2004.10.050 | s2cid = 14782686 | doi-access = free | bibcode = 2004CBio...14.1973D }}</ref> thereby widening the nuclear pore and allowing the entry of mitotic regulators.<ref>{{cite journal | vauthors = De Souza CP, Osmani SA | title = Mitosis, not just open or closed | journal = Eukaryotic Cell | volume = 6 | issue = 9 | pages = 1521–1527 | date = September 2007 | pmid = 17660363 | pmc = 2043359 | doi = 10.1128/EC.00178-07 }}</ref>

===Preservation of integrity===
In [[fungi]] undergoing [[Mitosis|closed mitosis]], where the nucleus remains intact, changes in the permeability barrier of the nuclear envelope are attributed to alterations within the NPC. These changes facilitate the entry of mitotic regulators into the nucleus. Studies in ''Aspergillys nidulans'' suggest that the NPC composition appears to be effected by the mitotiv kinase NIMA. NIMA potentially phosphorylates nucleoporins Nup98 and Gle2/Rae1, leading to NPC remodeling.<ref>{{cite journal |last1=Liu |first1=Hui-Lin |last2=De Souza |first2=Colin P.C. |last3=Osmani |first3=Aysha H. |last4=Osmani |first4=Stephen A. |title=The Three Fungal Transmembrane Nuclear Pore Complex Proteins of Aspergillus nidulans Are Dispensable in the Presence of an Intact An-Nup84-120 Complex |journal=Molecular Biology of the Cell |date=15 January 2009 |volume=20 |issue=2 |pages=616–630 |doi=10.1091/mbc.e08-06-0628 |pmid=19019988 |pmc=2626566 }}</ref> This remodeling allows the nuclear entry of the protein complex cdc2/cyclinB and various other proteins, including soluble tubulin. The NPC scaffold remains intact throughout the whole closed mitosis. This seems to preserve the integrity of the nuclear envelope.<ref>{{cite journal |last1=Kutay |first1=Ulrike |last2=Jühlen |first2=Ramona |last3=Antonin |first3=Wolfram |title=Mitotic disassembly and reassembly of nuclear pore complexes |journal=Trends in Cell Biology |date=December 2021 |volume=31 |issue=12 |pages=1019–1033 |doi=10.1016/j.tcb.2021.06.011 |pmid=34294532 |hdl=20.500.11850/518955 |hdl-access=free }}</ref>