The nuclear pore complex: a protein machine bridging the nucleus and cytoplasm

Ryan, Kathryn J.; Wente, Susan R.

doi:10.1016/s0955-0674(00)00101-0

Cited by 231 publications

(191 citation statements)

References 93 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…The kaps escort their cargos to the NPC, where the kaps bind to members of a family of nups that contain multiple phenylalanine-glycine (FG) repeat motifs within their primary structure. These repetitive peptides directly mediate the binding of the kaps to the FG-nups (reviewed in Ryan and Wente, 2000). Because these nups are located all along the channel through the NPC, most of the current transport models propose that the FG binding sites play an essential role in the movement of the kap/cargo complex through the NPC.…”

Section: Introductionmentioning

confidence: 99%

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

Hawryluk-Gara

Shibuya

Wozniak

2005

MBoC

125

149

View full text Add to dashboard Cite

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...

show abstract

Section: Introductionmentioning

confidence: 99%

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

Hawryluk-Gara

Shibuya

Wozniak

2005

MBoC

125

149

View full text Add to dashboard Cite

show abstract

“…The bidirectional exchange of macromolecules is mediated by the nuclear pore complex (NPC) 1 embedded in lipid bilayers of the nuclear envelope. NPC is one of the largest macromolecular assemblies that is currently known in eukaryotic cells, with an estimated mass of about 66 MDa, consisting of multiple copies of about 30 different proteins.…”

mentioning

confidence: 99%

β-Catenin Shows an Overlapping Sequence Requirement but Distinct Molecular Interactions for Its Bidirectional Passage through Nuclear Pores

Koike

Kose

Furuta

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

␤-Catenin is an example of a typical molecule that can be translocated bidirectionally through nuclear pore complexes (NPCs) on its own in a facilitated manner. In this work the nuclear import and export of ␤-catenin were examined to compare the sequence requirement of this molecule and to determine whether molecular interactions required for its bidirectional NPC passage are distinct or not. Deletion analysis of ␤-catenin revealed that armadillo repeats 10 -12 and the C terminus comprise the minimum region necessary for nuclear migration activity. Further dissection of this fragment showed that the C terminus tail plays an essential role in nuclear migration. The region of ␤-catenin required for export substantially overlapped the region required for import. Therefore, the NPC translocation of ␤-catenin is apparently reversible, which is consistent with findings reported previously. However, different translocating molecules blocked nuclear import and export of ␤-catenin differentially. The data herein indicate that ␤-catenin shows an overlapping sequence requirement for its import and export but that bidirectional movement through the NPC proceeds through distinct molecular interactions.

show abstract

“…Nuclear pores regulate vectorial import and export between the nucleus and cytoplasm. 7 Irregularity of NE shape, from any cause, could theoretically affect a number of cell physiologies. Nuclear lamina proteins are involved in determining replication competence 8 -14 and organizing transcription by binding to and segregating heterochromatin 15 (reviewed in 16 ).…”

mentioning

confidence: 99%

Nuclear Envelope Irregularity Is Induced by RET/PTC During Interphase

Fischer

Taysavang

Jhiang

2003

The American Journal of Pathology

View full text Add to dashboard Cite

Nuclear envelope (NE) irregularity is an important diagnostic feature of cancer, and its molecular basis is not understood. One possible cause is abnormal postmitotic NE re-assembly, such that a rounded contour is never achieved before the next mitosis. Alternatively, dynamic forces could deform the NE during interphase following an otherwise normal postmitotic NE re-assembly. To distinguish these possibilities, normal human thyroid epithelial cells were microinjected with the papillary thyroid carcinoma oncogene (RET/PTC1 short isoform, known to induce NE irregularity), an attenuated version of RET/PTC1 lacking the leucine zipper dimerization domain (RET/PTC1 ⌬zip), H (V-12) RAS, and labeled dextran. Cells were fixed at 6 or 18 to 24 hours, stained for lamins and the products of microinjected plasmids, and scored blindly using previously defined criteria for NE irregularity. 6.5% of non-injected thyrocytes showed NE irregularity. Neither dextran nor RAS microinjections increased NE irregularity. In contrast, RET/PTC1 microinjection induced NE irregularity in 27% of cells at 6 hours and 37% of cells at 18 to 24 hours. RET/PTC1 ⌬zip induced significantly less irregularity. Since irregularity develops quickly, and since no mitoses and only rare possible postmitotic cells were scored, postmitotic NE re-assembly does not appear necessary for RET/PTC signaling to induce an irregular NE contour. An irregularity in nuclear shape is a common diagnostic abnormality in cancer cells, yet surprisingly little is known about the structural basis of this change or its functional significance. The large-scale organization of the nuclear envelope (NE) defines nuclear shape. The NE consists of two lipid bilayers, nuclear pores, and the nuclear lamina (reviewed in 1-4 ). One lipid bilayer is the outer nuclear membrane, which is continuous with the endoplasmic reticulum. To date, no biochemical difference is known to distinguish the outer nuclear membrane or its membraneassociated proteins from the endoplasmic reticulum. In contrast, the inner nuclear membrane facing chromatin contains a number of membrane-associated proteins that are specific to this lipid bilayer. In turn, the membraneassociated proteins of the inner nuclear membrane are tightly associated with the intermediate filament proteins, called lamins, to form the chromatin-associated nuclear lamina. 2,5,6 The inner nuclear lipid bilayer is continuous with the outer nuclear membrane at nuclear pores. Nuclear pores regulate vectorial import and export between the nucleus and cytoplasm. 7 Irregularity of NE shape, from any cause, could theoretically affect a number of cell physiologies. Nuclear lamina proteins are involved in determining replication competence 8 -14 and organizing transcription by binding to and segregating heterochromatin 15 (reviewed in 16 ). Consistent with a role in organizing transcription, large-scale localization of genes near the NE is associated with transcriptional silencing. 17 Theoretically the function of nuclear pores could be altered within...

show abstract

The nuclear pore complex: a protein machine bridging the nucleus and cytoplasm

Cited by 231 publications

References 93 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

β-Catenin Shows an Overlapping Sequence Requirement but Distinct Molecular Interactions for Its Bidirectional Passage through Nuclear Pores

Nuclear Envelope Irregularity Is Induced by RET/PTC During Interphase

Contact Info

Product

Resources

About