Cell Cycle Regulated Transport Controlled by Alterations in the Nuclear Pore Complex

Makhnevych, Taras; Lusk, C. Patrick; Anderson, Andrea M.; Aitchison, John D.; Wozniak, Richard W.

doi:10.1016/s0092-8674(03)00986-3

Cited by 137 publications

(134 citation statements)

References 55 publications

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“…Nup53p binds to Nup170p during interphase, which blocks the ability of Nup53p to bind the karyopherin Kap121p. In contrast, during mitosis Nup53p is no longer detected in association with Nup170p but is instead bound to Nic96p and Kap121p (Makhnevych et al, 2003). How Nup59p, Nup157p, and Nup192p fit into this developing model is less clear.…”

Section: Discussionmentioning

confidence: 95%

“…Genetic and biochemical analyses have established that yeast Nup53p is part of a network of interacting nups that includes Nup170p, Nup59p, Nic96p, Nup157p, and Nup192p (Aitchison et al, 1995b;Marelli et al, 1998;Kosova et al, 1999;Fahrenkrog et al, 2000;Lusk et al, 2002;Makhnevych et al, 2003). A model for how these nups are organized within the NPC is beginning to emerge.…”

Section: Discussionmentioning

confidence: 99%

“…A model for how these nups are organized within the NPC is beginning to emerge. Nup53p can bind directly to Nup170p and Nic96p (Lusk et al, 2002;Makhnevych et al, 2003;Lusk and Wozniak, unpublished data). However, their interactions are cell cycle regulated.…”

Section: Discussionmentioning

confidence: 99%

“…A consequence of this rearrangement is the exposure of a binding site on Nup53p for the karyopherin Kap121p. Binding to Nup53p inhibits the translocation of Kap121p and its cargo into the nucleus, thus specifically regulating this pathway during mitosis (Makhnevych et al, 2003). Other examples of regulated changes in nup interactions have also been observed in Aspergillus nidulans (De Souza et al, 2004).…”

Section: Introductionmentioning

confidence: 93%

“…This, in fact, appears to be the case for a yeast subcomplex consisting of the nonrepeat nup Nup170p and the FG-nup Nup53p. The interactions between these nups are altered during the cell cycle (Makhnevych et al, 2003). In interphase, Nup53p interacts with Nup170p but is not detected in association with Nic96p.…”

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confidence: 99%

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Vertebrate Nup53 Interacts with the Nuclear Lamina and Is Required for the Assembly of a Nup93-containing Complex

Hawryluk-Gara

Shibuya

Wozniak

2005

MBoC

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125

149

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The nuclear pore complex (NPC) is an evolutionarily conserved structure that mediates exchange of macromolecules across the nuclear envelope (NE). It is comprised of ϳ30 proteins termed nucleoporins that are each present in multiple copies. We have investigated the function of the human nucleoporin Nup53, the ortholog of Saccharomyces cerevisiae Nup53p. Both cell fractionation and in vitro binding data suggest that Nup53 is tightly associated with the NE membrane and the lamina where it interacts with lamin B. We have also shown that Nup53 is capable of physically interacting with a group of nucleoporins including Nup93, Nup155, and Nup205. Consistent with this observation, depletion of Nup53 using small interfering RNAs causes a decrease in the cellular levels of these nucleoporins as well as the spindle checkpoint protein Mad1, likely due to destabilization of Nup53-containing complexes. The cellular depletion of this group of nucleoporins, induced by depleting either Nup53 or Nup93, severely alters nuclear morphology producing phenotypes similar to that previously observed in cells depleted of lamin A and Mad1. On basis of these data, we propose a model in which Nup53 is positioned near the pore membrane and the lamina where it anchors an NPC subcomplex containing Nup93, Nup155, and Nup205. INTRODUCTIONThe nuclear envelope (NE) is a specialized membrane system that functions to separate the eukaryotic genome from the cytoplasm. The NE consists of an inner and an outer nuclear membrane. The former contains a distinct set of associated proteins, whereas the latter is structurally equivalent to the endoplasmic reticulum (reviewed in Mattaj, 2004). The nucleoplasmic face of the metazoan inner nuclear membrane is connected to a fibrous protein meshwork termed the nuclear lamina that forms a shell around the underlying chromatin mass. The lamina is composed of Aand B-type lamins, which are closely related to one another and to the intermediate filament-like family of proteins (reviewed in Burke, 2001). The nuclear lamina has been suggested to be involved in maintaining the structural integrity of the NE and influencing chromatin structure and function. The association of the lamina with transcriptionally inactive heterochromatin has led to the suggestion that it may play a role in regulating gene expression and some recent data support this idea (reviewed in Mattout-Drubezki and Gruenbaum, 2003).At numerous points along the NE the inner and outer nuclear membranes fuse to form pores ϳ100 nm in diameter. These pores are occupied by complex macromolecular structures termed nuclear pore complexes (NPCs). The NPCs are associated with euchromatin channels that extend into the interior of the nucleus, interrupting the continuity of the lamina and the heterochromatin. These complex structures have an estimated mass of ϳ60 million Daltons, but are composed of a relatively small number of proteins (ϳ30; Rout et al., 2000;Cronshaw et al., 2002) termed nucleoporins or nups. This is explained by the fact that all of these prot...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

mentioning

confidence: 99%

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Vertebrate Nup53 Interacts with the Nuclear Lamina and Is Required for the Assembly of a Nup93-containing Complex

Hawryluk-Gara

Shibuya

Wozniak

2005

MBoC

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125

149

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Nuclear‐Cytoplasmic Transport

McPherson

Lange

Doetsch

et al. 2009

Encyclopedia of Life Sciences

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In eukaryotic cells, the genomic deoxyribonucleic acid (DNA) in the nucleus is separated from the translational machinery in the cytoplasm by the nuclear envelope. Transport of macromolecules such as proteins and ribonucleic acid (RNA) across this membrane is essential for cellular function and requires active nuclear–cytoplasmic transport systems. These systems consist of soluble transport receptors, which recognize and bind cargo in one compartment, mediate transport through nuclear pore complexes embedded in the nuclear envelope and deliver cargo in the target compartment. Disruption of this highly regulated process results in abnormal cell function and is linked to human disease etiology. Understanding the contribution of nuclear protein and RNA transport to cellular organization is one of the major challenges in cell biology. Key Concepts Transport into and out of the nucleus occurs through nuclear pore complexes (NPCs), which are large proteinaceous channels that perforate the nuclear membrane. Proteins destined for import into the nucleus contain a nuclear localization signal (NLS) and proteins destined for export from the nucleus contain a nuclear export signal (NES), each of which targets them for transport. Soluble transport receptors called importins and exportins or karyopherins recognize and bind macromolecular cargos and facilitate transport through the nuclear pore. The asymmetric distribution of RanGDP in the cytoplasm and RanGTP in the nucleus controls the directionality of nuclear transport. Nuclear protein import can be regulated through inter‐ or intramolecular occlusion of the NLS or NES; posttranslation modification of the targeting signal; compartmental sequestration of the cargo protein or altering properties of the nuclear transport machinery including receptors and nuclear pores. Many classes of RNA are transported via Ran‐regulated, karyopherin‐dependent pathways. Messenger ribonucleic acid (mRNA) export is highly coupled to mRNA processing and is mediated by distinct receptors. Mutations in nuclear targeting signals and nuclear transport receptors have been linked to several human diseases.

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Nuclear–Cytoplasmic Transport

McPherson

Lange

Doetsch

et al. 2015

Encyclopedia of Life Sciences

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In eukaryotic cells, the genomic DNA in the nucleus is separated from the translational machinery in the cytoplasm by the nuclear envelope. Transport of macromolecules such as proteins and RNA across this membrane is essential for cellular function and requires active nuclear–cytoplasmic transport systems. These systems consist of soluble transport receptors, which recognise and bind cargo in one compartment, mediate transport through nuclear pore complexes embedded in the nuclear envelope and deliver cargo in the target compartment. Disruption of this highly regulated process results in abnormal cell function and is linked to human disease aetiology. Understanding the contribution of nuclear protein and RNA transport to cellular organisation is one of the major challenges in cell biology. Key Concepts Transport into and out of the nucleus is mediated by nuclear pore complexes (NPCs), which are large proteinaceous channels that perforate the nuclear membrane. Proteins destined for import into the nucleus contain a nuclear localisation signal (NLS) and proteins destined for export from the nucleus contain a nuclear export signal (NES), each of which targets them for transport. Soluble transport receptors called importins and exportins or karyopherins recognise and bind macromolecular cargos and facilitate transport through nuclear pore complexes. The asymmetric distribution of RanGDP in the cytoplasm and RanGTP in the nucleus controls the directionality of nuclear transport. Nuclear protein transport can be regulated through inter‐ or intramolecular occlusion of the NLS or NES, post‐translation modification of the targeting signal, compartmental sequestration of the cargo protein or altering properties of the nuclear transport machinery including receptors and nuclear pores. Many classes of RNA are transported via Ran‐regulated, karyopherin‐dependent pathways. mRNA export is highly coupled to mRNA processing and is mediated by distinct receptors. Mutations in nuclear targeting signals and nuclear transport receptors have been linked to several human diseases.

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Cell Cycle Regulated Transport Controlled by Alterations in the Nuclear Pore Complex

Cited by 137 publications

References 55 publications

Vertebrate Nup53 Interacts with the Nuclear Lamina and Is Required for the Assembly of a Nup93-containing Complex

Vertebrate Nup53 Interacts with the Nuclear Lamina and Is Required for the Assembly of a Nup93-containing Complex

Nuclear‐Cytoplasmic Transport

Nuclear–Cytoplasmic Transport

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