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The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth

Journal

CELLS
Volume 11, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/cells11091456

Keywords

nuclear pore complex; nucleoporin; NPC; membrane fusion; Ran; lipids; assembly factor; amphipathic helix; nuclear transport receptor; FG repeats; Brl1; autophagy; ageing; aggregation; neurodegneration

Categories

Funding

  1. ETH research grant [ETH-33 19-1]
  2. Research Council of Norway [NFR 315615]
  3. Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [SNSF 310030_207453]

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Nuclear pore complexes (NPCs) are transport channels that cross the nuclear envelope and are composed of nucleoporin proteins. While the overall structure and inventory of nucleoporins are conserved, the composition and assembly pathways of NPCs exhibit significant variability. NPCs appear to be unexchangeable in post-mitotic cells. There are unresolved questions regarding the versatility of NPC assembly and composition, as well as how cells monitor their functional state.
Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from similar to 500-1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle.

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