The Conserved Transmembrane Nucleoporin NDC1 Is Required for Nuclear Pore Complex Assembly in Vertebrate Cells

Mansfeld, Jörg; Güttinger, Stephan; Hawryluk-Gara, Lisa A.; Panté, Nelly; Mall, Moritz; Galy, Vincent; Haselmann, Uta; Mühlhäusser, Petra; Wozniak, Richard W.; Mattaj, Iain W.; Kutay, Ulrike; Antonin, Wolfram

doi:10.1016/j.molcel.2006.02.015

Cited by 217 publications

(305 citation statements)

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“…In addition, in vitro depletion of NDC1, a conserved transmembrane Nup, results in identical NE assembly defects as observed for POM121 and Nup155, where the NE membrane vesicles are docked to the chromatin but not fused (Mansfeld et al, 2006). Although studies examining the depletion of NDC1 from cultured mammalian cells suggest a critical role for NDC1 on NPC assembly, they further imply that the protein is not absolutely essential for NE formation (Mansfeld et al, 2006;Stavru et al, 2006). Both Nup155 and NDC1 form evolutionarily conserved interactions with the nucleoporin Nup53 (Hawryluk- Gara et al, 2005;Mansfeld et al, 2006).…”

Section: Introductionmentioning

confidence: 68%

“…This suggests that Nup155, like POM121 and the Nup107-160 complex, plays a critical role both in NE assembly and in the proposed NPC/NE assembly checkpoint. In addition, in vitro depletion of NDC1, a conserved transmembrane Nup, results in identical NE assembly defects as observed for POM121 and Nup155, where the NE membrane vesicles are docked to the chromatin but not fused (Mansfeld et al, 2006). Although studies examining the depletion of NDC1 from cultured mammalian cells suggest a critical role for NDC1 on NPC assembly, they further imply that the protein is not absolutely essential for NE formation (Mansfeld et al, 2006;Stavru et al, 2006).…”

mentioning

confidence: 86%

“…GST-Nup53 chimeras were constructed precisely as described previously (Mansfeld et al, 2006). Expression and purification have been previously described in detail (Hawryluk-Gara et al, 2005).…”

Section: Gst-pulldown Assaymentioning

confidence: 99%

“…Antibodies against Nup53 (Hawryluk-Gara et al, 2005), Nup155 , and Nup205 (Krull et al, 2004;Mansfeld et al, 2006) have been described previously. Other antibodies used were mAb414 (BAbCO, Richmond, CA), anti-glutathione transferase (GST) (Abcam, Cambridge, MA), and fluorescently labeled secondary antibodies used for immunofluorescence (Jackson ImmunoResearch Laboratories, West Grove, PA).…”

Section: Antibodiesmentioning

confidence: 99%

“…Although studies examining the depletion of NDC1 from cultured mammalian cells suggest a critical role for NDC1 on NPC assembly, they further imply that the protein is not absolutely essential for NE formation (Mansfeld et al, 2006;Stavru et al, 2006). Both Nup155 and NDC1 form evolutionarily conserved interactions with the nucleoporin Nup53 (Hawryluk- Gara et al, 2005;Mansfeld et al, 2006). These interactions suggest Nup53 may function as a bridge point between the NPC core and the pore membrane, a strategic location to influence NE and NPC biogenesis.…”

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confidence: 99%

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Nup53 Is Required for Nuclear Envelope and Nuclear Pore Complex Assembly

Hawryluk-Gara

Platani

Santarella

et al. 2008

MBoC

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Transport across the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs). These structures are composed of various subcomplexes of proteins that are each present in multiple copies and together establish the eightfold symmetry of the NPC. One evolutionarily conserved subcomplex of the NPC contains the nucleoporins Nup53 and Nup155. Using truncation analysis, we have defined regions of Nup53 that bind to neighboring nucleoporins as well as those domains that target Nup53 to the NPC in vivo. Using this information, we investigated the role of Nup53 in NE and NPC assembly using Xenopus egg extracts. We show that both events require Nup53. Importantly, the analysis of Nup53 fragments revealed that the assembly activity of Nup53 depleted extracts could be reconstituted using a region of Nup53 that binds specifically to its interacting partner Nup155. On the basis of these results, we propose that the formation of a Nup53-Nup155 complex plays a critical role in the processes of NPC and NE assembly. INTRODUCTIONThe nuclear envelope (NE) provides a physical barrier between the nucleus and cytoplasm and their unique metabolic tasks. The NE is defined by three morphologically distinct regions. The outer nuclear membrane (ONM) is continuous with the rough endoplasmic reticulum (ER) and contains a similar set of proteins (reviewed in Mattaj, 2004). The inner nuclear membrane (INM) lies adjacent to the nucleoplasm and contains a unique repertoire of proteins that, in part, mediate its interactions with the nuclear lamina and chromatin. Finally, at numerous locations along the NE, the ONM and INM are interrupted by pores where the INM and the ONM are bridged by a connecting membrane termed the pore membrane (POM) domain. Within these pores reside the nuclear pore complexes (NPCs), aqueous channels that provide portals for both passive and active transport of macromolecules.An NPC contains ϳ30 nucleoporins (Nups), many of which are evolutionarily conserved in structure and function (Tran and Wente, 2006). In many cases these Nups are organized into subcomplexes that are present in multiple copies, and they are distributed around the central axis of the NPC, contributing to its characteristic eightfold symmetry. Different groups of Nups and their respective subcomplexes contribute to distinct structural components of the NPC. For example, Nup214/Nup84 are components of the cytoplasmic fibrils (Kraemer et al., 1994;Bastos et al., 1997), the Nup53/Nup155 complex is part of the central core (Marelli et al., 1998), and Nup153 and Tpr contribute to the nucleoplasmic ring and fibrils (Krull et al., 2004).When metazoan cells enter mitosis, their NE is disassembled allowing for the mitotic spindle to access the condensed chromatin. Several models based on previous findings have been proposed to explain the mechanism by which this occurs (reviewed in Hetzer et al., 2005). NE disassembly is accompanied by the phosphorylation of multiple NE proteins including the lamins and several Nups (Burke and Ellenberg, 2002, and refer...

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Section: Introductionmentioning

confidence: 68%

mentioning

confidence: 86%

Section: Gst-pulldown Assaymentioning

confidence: 99%

Section: Antibodiesmentioning

confidence: 99%

mentioning

confidence: 99%

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Nup53 Is Required for Nuclear Envelope and Nuclear Pore Complex Assembly

Hawryluk-Gara

Platani

Santarella

et al. 2008

MBoC

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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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Puzzling out nuclear pore complex assembly

Penzo,

Palancade

2023

FEBS Letters

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Nuclear pore complexes (NPCs) are sophisticated multiprotein assemblies embedded within the nuclear envelope and controlling the exchanges of molecules between the cytoplasm and the nucleus. In this review, we summarize the mechanisms by which these elaborate complexes are built from their subunits, the nucleoporins, based on our ever‐growing knowledge of NPC structural organization and on the recent identification of additional features of this process. We present the constraints faced during the production of nucleoporins, their gathering into oligomeric complexes, and the formation of NPCs within nuclear envelopes, and review the cellular strategies at play, from co‐translational assembly to the enrolment of a panel of cofactors. Remarkably, the study of NPCs can inform our perception of the biogenesis of multiprotein complexes in general – and vice versa.

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The Conserved Transmembrane Nucleoporin NDC1 Is Required for Nuclear Pore Complex Assembly in Vertebrate Cells

Cited by 217 publications

References 34 publications

Nup53 Is Required for Nuclear Envelope and Nuclear Pore Complex Assembly

Nup53 Is Required for Nuclear Envelope and Nuclear Pore Complex Assembly

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

Puzzling out nuclear pore complex assembly

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