Ran GTPase in Nuclear Envelope Formation and Cancer Metastasis

2014 ◽  
pp. 323-351 ◽  
Author(s):  
Kyle B. Matchett ◽  
Suzanne McFarlane ◽  
Sophie E. Hamilton ◽  
Yousef S. A. Eltuhamy ◽  
Matthew A. Davidson ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Cancer Metastasis ◽  
Ran Gtpase ◽  
Nuclear Envelope Formation

Targeting of Ran: variation on a common theme?

2001 ◽  
Vol 114 (18) ◽  
pp. 3233-3241 ◽  
Author(s):  
Markus Künzler ◽  
Ed Hurt
Keyword(s):  
Nuclear Envelope ◽  
Mitotic Spindle ◽  
Nucleocytoplasmic Transport ◽  
Common Theme ◽  
Spindle Formation ◽  
Ran Gtpase ◽  
Cellular Processes ◽  
Important Target ◽  
Transport Receptors ◽  
Nuclear Envelope Formation

The Ran GTPase plays a key role in nucleocytoplasmic transport. In its GTP-bound form, it directly interacts with members of the importin β family of nuclear transport receptors and modulates their association with cargo. Work in cell-free higher-eukaryote systems has demonstrated additional roles for Ran in spindle and nuclear envelope formation during mitosis. However, until recently, no Ran-target proteins in these cellular processes were known. Several groups have now identified importin β as one important target of Ran during mitotic spindle formation. This finding suggests that Ran uses the same effectors to regulate different cellular processes.

scholarly journals Ran GTPase Cycle and Importins α and β Are Essential for Spindle Formation and Nuclear Envelope Assembly in LivingCaenorhabditis elegans Embryos

2002 ◽  
Vol 13 (12) ◽  
pp. 4355-4370 ◽  
Author(s):  
Peter Askjaer ◽  
Vincent Galy ◽  
Eva Hannak ◽  
Iain W. Mattaj
Keyword(s):  
Nuclear Envelope ◽  
Cell Function ◽  
Small Gtpase ◽  
Spindle Formation ◽  
Ran Gtpase ◽  
Early Embryos ◽  
Nuclear Envelope Assembly ◽  
Importin Α ◽  
Gtpase Cycle

The small GTPase Ran has been found to play pivotal roles in several aspects of cell function. We have investigated the role of the Ran GTPase cycle in spindle formation and nuclear envelope assembly in dividing Caenorhabditis elegans embryos in real time. We found that Ran and its cofactors RanBP2, RanGAP, and RCC1 are all essential for reformation of the nuclear envelope after cell division. Reducing the expression of any of these components of the Ran GTPase cycle by RNAi leads to strong extranuclear clustering of integral nuclear envelope proteins and nucleoporins. Ran, RanBP2, and RanGAP are also required for building a mitotic spindle, whereas astral microtubules are normal in the absence of these proteins. RCC1(RNAi) embryos have similar abnormalities in the initial phase of spindle formation but eventually recover to form a bipolar spindle. Irregular chromatin structures and chromatin bridges due to spindle failure were frequently observed in embryos where the Ran cycle was perturbed. In addition, connection between the centrosomes and the male pronucleus, and thus centrosome positioning, depends upon the Ran cycle components. Finally, we have demonstrated that both IMA-2 and IMB-1, the homologues of vertebrate importin α and β, are essential for both spindle assembly and nuclear formation in early embryos.

Three proteins required for early steps in the protein secretory pathway also affect nuclear envelope structure and cell cycle progression in fission yeast

2002 ◽  
Vol 115 (2) ◽  
pp. 421-431
Author(s):  
Anna Matynia ◽  
Sandra S. Salus ◽  
Shelley Sazer
Keyword(s):  
Cell Cycle ◽  
Nuclear Envelope ◽  
Fission Yeast ◽  
Cell Cycle Progression ◽  
Secretory Pathway ◽  
Yeast Cells ◽  
Ran Gtpase ◽  
A Cell ◽  
Cell Cycle Block ◽  
Er Membrane

The Ran GTPase is an essential protein that has multiple functions in eukaryotic cells. Fission yeast cells in which Ran is misregulated arrest after mitosis with condensed, unreplicated chromosomes and abnormal nuclear envelopes. The fission yeast sns mutants arrest with a similar cell cycle block and interact genetically with the Ran system. sns-A10, sns-B2 and sns-B9 have mutations in the fission yeast homologues of S. cerevisiae Sar1p, Sec31p and Sec53p, respectively, which are required for the early steps of the protein secretory pathway. The three sns mutants accumulate a normally secreted protein in the endoplasmic reticulum (ER), have an increased amount of ER membrane, and the ER/nuclear envelope lumen is dilated. Neither a post-ER block in the secretory pathway, nor ER proliferation caused by overexpression of an integral ER membrane protein, results in a cell cycle-specific defect. Therefore, the arrest seen in sns-A10, sns-B2 and sns-B9 is most likely due to nuclear envelope defects that render the cells unable to re-establish the interphase organization of the nucleus after mitosis. As a consequence, these mutants are unable to decondense their chromosomes or to initiate of the next round of DNA replication.

scholarly journals Role for phosphatidylinositol in nuclear envelope formation

2001 ◽  
Vol 356 (2) ◽  
pp. 495 ◽  
Author(s):  
Banafshé LARIJANI ◽  
Teresa M. BARONA ◽  
Dominic L. POCCIA
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Envelope Formation

scholarly journals Reshaping of the endoplasmic reticulum limits the rate for nuclear envelope formation

2008 ◽  
Vol 182 (5) ◽  
pp. 911-924 ◽  
Author(s):  
Daniel J. Anderson ◽  
Martin W. Hetzer
Keyword(s):  
Endoplasmic Reticulum ◽  
Nuclear Envelope ◽  
Mammalian Cells ◽  
Time Lapse ◽  
Principal Mechanism ◽  
Nuclear Assembly ◽  
Nuclear Envelope Formation ◽  
Rate Limiting

During mitosis in metazoans, segregated chromosomes become enclosed by the nuclear envelope (NE), a double membrane that is continuous with the endoplasmic reticulum (ER). Recent in vitro data suggest that NE formation occurs by chromatin-mediated reorganization of the tubular ER; however, the basic principles of such a membrane-reshaping process remain uncharacterized. Here, we present a quantitative analysis of nuclear membrane assembly in mammalian cells using time-lapse microscopy. From the initial recruitment of ER tubules to chromatin, the formation of a membrane-enclosed, transport-competent nucleus occurs within ∼12 min. Overexpression of the ER tubule-forming proteins reticulon 3, reticulon 4, and DP1 inhibits NE formation and nuclear expansion, whereas their knockdown accelerates nuclear assembly. This suggests that the transition from membrane tubules to sheets is rate-limiting for nuclear assembly. Our results provide evidence that ER-shaping proteins are directly involved in the reconstruction of the nuclear compartment and that morphological restructuring of the ER is the principal mechanism of NE formation in vivo.

scholarly journals A trypsin-sensitive receptor on membrane vesicles is required for nuclear envelope formation in vitro.

1988 ◽  
Vol 107 (1) ◽  
pp. 57-68 ◽  
Author(s):  
K L Wilson ◽  
J Newport
Keyword(s):  
Nuclear Envelope ◽  
Protein Interactions ◽  
Membrane Vesicles ◽  
Integral Membrane Protein ◽  
Electron Microscopic ◽  
Vitro Assay ◽  
Nuclear Envelope Assembly ◽  
Microscopic Studies ◽  
Nuclear Envelope Formation

The reformation of functioning organelles at the end of mitosis presents a problem in vesicle targeting. Using extracts made from Xenopus laevis frog eggs, we have studied in vitro the vesicles that reform the nuclear envelope. In the in vitro assay, nuclear envelope growth is linear with time. Furthermore, the final surface area of the nuclear envelopes formed is directly dependent upon the amount of membrane vesicles added to the assay. Egg membrane vesicles could be fractionated into two populations, only one of which was competent for nuclear envelope assembly. We found that vesicles active in nuclear envelope assembly contained markers (BiP and alpha-glucosidase II) characteristic of the endoplasmic reticulum (ER), but that the majority of ER-derived vesicles do not contribute to nuclear envelope size. This functional distinction between nuclear vesicles and ER-derived vesicles implies that nuclear vesicles are unique and possess at least one factor required for envelope assembly that is lacking in other vesicles. Consistent with this, treatment of vesicles with trypsin destroyed their ability to form a nuclear envelope; electron microscopic studies indicate that the trypsin-sensitive proteins is required for vesicles to bind to chromatin. However, the protease-sensitive component(s) is resistant to treatments that disrupt protein-protein interactions, such as high salt, EDTA, or low ionic strength solutions. We propose that an integral membrane protein, or protein tightly associated with the membrane, is critical for nuclear vesicle targeting or function.

Nuclear envelope localization of Ran-binding protein 2 and Ran-GTPase-activating protein 1 in psoriatic epidermal keratinocytes

2014 ◽  
Vol 23 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Kayo Yasuda ◽  
Kazumitsu Sugiura ◽  
Takuya Takeichi ◽  
Yasushi Ogawa ◽  
Yoshinao Muro ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Binding Protein ◽  
Epidermal Keratinocytes ◽  
Gtpase Activating Protein ◽  
Ran Gtpase

scholarly journals PROPHASING OF INTERPHASE NUCLEI AND INDUCTION OF NUCLEAR ENVELOPES AROUND METAPHASE CHROMOSOMES IN HELA AND CHINESE HAMSTER HOMO- AND HETEROKARYONS

1974 ◽  
Vol 62 (1) ◽  
pp. 104-113 ◽  
Author(s):  
Yoshitaka Obara ◽  
Lee S. Chai ◽  
Herbert Weinfeld ◽  
Avery A. Sandberg
Keyword(s):  
Nuclear Envelope ◽  
Hela Cells ◽  
Interphase Nucleus ◽  
Chinese Hamster ◽  
Binucleate Cell ◽  
Metaphase Chromosomes ◽  
Interphase Nuclei ◽  
Multinucleate Cells ◽  
Interphase Cells ◽  
Nuclear Envelope Formation

Fusing human HeLa metaphase cells with HeLa interphase cells resulted within 30 min in either of two phenomena in the resultant binucleate cell: either prophasing of the interphase nucleus or formation of a normal-appearing nuclear envelope around the metaphase chromosomes. The frequency of either occurrence was strongly dependent on environmental pH. At pH's of 6.6–8.0, prophasing predominated; at pH 8.5 nuclear envelope formation predominated. Additionally, the frequencies of the two events in multinucleate cells depended on the metaphase/interphase ratio. When the ratio was 0.33 nuclear envelope formation predominated; when it was 2.0 prophasing predominated. In their general features, the results with fused HeLa cells resembled those reported earlier with fused Chinese hamster Don cells. However, the results provided an indication that between pH 6.6 and 8.0 the HeLa metaphase cells possessed a much greater capacity than the Don metaphase cells to induce prophasing. Fusion of Don metaphase cells with HeLa interphase cells or of Don interphase cells with HeLa metaphase cells at pH 8.0 resulted in nuclear envelope formation or prophasing in each kind of heterokaryon. As in the homokaryons, the frequencies of the two events in the heterokaryons depended on the metaphase/interphase ratio. The statistics of prophasing and nuclear envelope formation in the homo- and heterokaryon populations were consistent with the notion that disruption or formation of the nuclear envelope depends on the balance attained between disruptive and formative processes.

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