Postmitotic nuclear pore assembly proceeds by radial dilation of small ER membrane openings

Otsuka, Shotaro; Steyer, Anna M.; Schorb, Martin; Hèriché, Jean-Karim; Hossain, M. Julius; Sethi, Suruchi; Schwab, Yannick; Beck, Martin; Ellenberg, Jan

doi:10.1101/141150

Cited by 3 publications

(23 citation statements)

References 37 publications

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“…Such prepores contained dense material in the center of the holes as well as nuclear ring-like structures underneath them. The small membrane hole then dilated as the inner ring, and the cytoplasmic ring formed and the density of central channel increased [24]. The molecular and structural progression of postmitotic NPC assembly described in this section is summarized in Fig.…”

Section: Mechanism Of Npc Assembly In the Reforming Nuclear Membranementioning

confidence: 91%

“…Two distinct assembly mechanisms of the NPC . (A) Postmitotic NPC assembly proceeds by a radial dilation of small membrane openings . The initial prepore contains dense material in the center of the membrane hole as well as the nuclear ring.…”

Section: Postmitotic Ne and Npc Assemblymentioning

confidence: 99%

“…These differences may depend on the abundance of ER membranes as well as of ER-shaping proteins, including reticulons, GTPases atlastins, and the protein lunapark [52,53]. More recently, a time course of EM reconstructions of entire HeLa cells from early to late anaphase by correlative live imaging with large volume EM could capture the dynamic process of covering chromosomes with ER-derived nuclear membranes at nanometer [24]. This study showed that the NE forms from highly fenestrated ER sheets that contain a large number of discontinuities whose diameter shrinks as NE assembly proceeds.…”

Section: Mechanism Of Nuclear Membrane Coverage Of Chromosomes Duringmentioning

confidence: 99%

“…They have shown that ELYS, the Nup107-160 complex, and the nucleoplasmic Nup153 are recruited in late anaphase and that the cytoplasmic Nup214 and the nuclear basket component TPR are recruited later at telophase. In addition to these studies, live cell imaging in both rat and human cells has directly visualized the dynamic process of Nup recruitment to the NE and shown that postmitotic NPC assembly indeed proceeds by sequential addition of Nups in an overall similar order to the one proposed by the in vitro and immuno-localization studies [20][21][22][23][24]. While the order of postmitotic Nup recruitment to the chromosome surface is well defined with few exceptions, which structural intermediates are formed in order to build a mature NPC remained mysterious for a long time.…”

Section: Mechanism Of Npc Assembly In the Reforming Nuclear Membranementioning

confidence: 99%

“…fusion Vertical and lateral growth ONM INM • RanGTP-induced release of Nups/INM proteins from importin β • Cell-cycle dependent dephosphorylation of Nups/INM proteins Hole shrinkage Two distinct assembly mechanisms of the NPC. (A) Postmitotic NPC assembly proceeds by a radial dilation of small membrane openings[24]. The initial prepore contains dense material in the center of the membrane hole as well as the nuclear ring.…”

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confidence: 99%

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Mechanisms of nuclear pore complex assembly – two different ways of building one molecular machine

2017

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The nuclear pore complex (NPC) mediates all macromolecular transport across the nuclear envelope. In higher eukaryotes that have an open mitosis, NPCs assemble at two points in the cell cycle: during nuclear assembly in late mitosis and during nuclear growth in interphase. How the NPC, the largest nonpolymeric protein complex in eukaryotic cells, self‐assembles inside cells remained unclear. Recent studies have started to uncover the assembly process, and evidence has been accumulating that postmitotic and interphase NPC assembly use fundamentally different mechanisms; the duration, structural intermediates, and regulation by molecular players are different and different types of membrane deformation are involved. In this Review, we summarize the current understanding of these two modes of NPC assembly and discuss the structural and regulatory steps that might drive the assembly processes. We furthermore integrate understanding of NPC assembly with the mechanisms for rapid nuclear growth in embryos and, finally, speculate on the evolutionary origin of the NPC implied by the presence of two distinct assembly mechanisms.

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Section: Mechanism Of Npc Assembly In the Reforming Nuclear Membranementioning

confidence: 91%

Section: Postmitotic Ne and Npc Assemblymentioning

confidence: 99%

Section: Mechanism Of Nuclear Membrane Coverage Of Chromosomes Duringmentioning

confidence: 99%

Section: Mechanism Of Npc Assembly In the Reforming Nuclear Membranementioning

confidence: 99%

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confidence: 99%

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Mechanisms of nuclear pore complex assembly – two different ways of building one molecular machine

2017

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Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane openings

Otsuka

Steyer

Schorb

et al. 2017

Nat Struct Mol Biol

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104

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The nuclear envelope has to be reformed after mitosis to create viable daughter cells with closed nuclei. How membrane sealing of DNA and assembly of nuclear pore complexes (NPCs) are achieved and coordinated is poorly understood. Here, we reconstructed nuclear membrane topology and the structures of assembling NPCs in a correlative 3D EM time course of dividing human cells. Our quantitative ultrastructural analysis shows that nuclear membranes form from highly fenestrated ER sheets whose holes progressively shrink. NPC precursors are found in small membrane holes and dilate radially during assembly of the inner ring complex, forming thousands of transport channels within minutes. This mechanism is fundamentally different from that of interphase NPC assembly and explains how mitotic cells can rapidly establish a closed nuclear compartment while making it transport competent.

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Artificial intelligence reveals nuclear pore complexity

Mosalaganti

Obarska-Kosińska

Siggel

et al. 2021

Preprint

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Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport. Their intricate 120 MDa architecture remains incompletely understood. Here, we report a near-complete structural model of the human NPC scaffold with explicit membrane and in multiple conformational states. We combined AI-based structure prediction with in situ and in cellulo cryo-electron tomography and integrative modeling. We show that linker Nups spatially organize the scaffold within and across subcomplexes to establish the higher-order structure. Microsecond-long molecular dynamics simulations suggest that the scaffold is not required to stabilize the inner and outer nuclear membrane fusion, but rather widens the central pore. Our work exemplifies how AI-based modeling can be integrated with in situ structural biology to understand subcellular architecture across spatial organization levels.One sentence summaryAn AI-based, dynamic model of the human nuclear pore complex reveals how the protein scaffold and the nuclear envelope are coupled inside cells.

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Postmitotic nuclear pore assembly proceeds by radial dilation of small ER membrane openings

Abstract: 18The nuclear envelope has to be reformed after mitosis to create viable daughter cells with closed

Cited by 3 publications

References 37 publications

Mechanisms of nuclear pore complex assembly – two different ways of building one molecular machine

Mechanisms of nuclear pore complex assembly – two different ways of building one molecular machine

Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane openings

Artificial intelligence reveals nuclear pore complexity

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