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

Abstract 191: Ras GTPase-activating Protein SH3 Domain Binding Protein 1 (G3BP1) Regulates The Induction Of Stress Granules During Cardiac Hypertrophy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Danish Sayed
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Myocytes ◽  
Posttranscriptional Regulation ◽  
Binding Protein ◽  
Stress Granules ◽  
Sh3 Domain ◽  
Gtpase Activating Protein ◽  
Ras Gtpase ◽  
Mrna Binding

Stress granules (SGs) are dynamic, microscopically visible, cytoplasmic bodies that play a major role in mRNA metabolism (e.g. sorting, storage, decay) and induced in cells during stress conditions like starvation, oxidative strain or growth. With substantial role in cancer and neurodegenerative diseases, these granules have never been studied during cardiac hypertrophy, or in the heart in general. Several studies have identified independent proteins, mostly mRNA binding proteins that are part of these granules, some of which are sufficient to nucleate the assembly in quiescent cells even without stress. One such mRNA binding protein is Ras GTPase-activating protein SH3 domain binding protein 1 (G3BP1), which increases during cardiac hypertrophy via posttranscriptional regulation. Thus, we hypothesized that G3BP1 might be involved in the induction of SGs during hypertrophy and hence in regulating mRNA processing and gene expression. Our aim was to investigate, 1) if these SGs appear in hypertrophied hearts and 2) if G3BP1 is necessary and sufficient to induce them during hypertrophic stimuli. In vivo staining of TIA-1/TIAR (SG marker) in mouse hearts subjected to sham or transaortic coarctation (TAC) surgeries showed accumulation of these granules with cardiac hypertrophy. Similar induction was seen in isolated, cultured, rat neonatal cardiac myocytes with hypertrophic stimulation (Endothelin1) or overexpression of G3BP1 alone (>60% of myocytes stained for SG). Conversely, switch to growth-inhibited conditions or knockdown of G3BP1 in hypertrophying myocytes was sufficient to prevent the assembly of these structures. Co-staining with other components of these granules like TIA-1/TIAR or proteins specific to P bodies, like decapping enzyme 1 validated these structures as SGs in cardiac myocytes. Interestingly, a long non-coding RNA, Gas5 (Growth Arrest Specific 5) that is validated binding partner of G3BP1 sequestered to perinuclear focal locations in myocytes stimulated with ET1, suggesting growth-induced recruitment to SGs. While we are still in process of examining G3BP1 targets that are recruited to SGs and their role in hypertrophy development, we have concluded that G3BP1 is required for the induction of SGs during cardiac hypertrophy

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.

scholarly journals Nuclear RanGAP Is Required for the Heterochromatin Assembly and Is Reciprocally Regulated by Histone H3 and Clr4 Histone Methyltransferase in Schizosaccharomyces pombe

2006 ◽  
Vol 17 (6) ◽  
pp. 2524-2536 ◽  
Author(s):  
Hitoshi Nishijima ◽  
Jun-ichi Nakayama ◽  
Tomoko Yoshioka ◽  
Ayumi Kusano ◽  
Hideo Nishitani ◽  
...  
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Histone H3 ◽  
Inhibitory Effect ◽  
Stable Complex ◽  
Gtpase Activating Protein ◽  
Ran Gtpase ◽  
The Core ◽  
Trimeric Complex ◽  
Core Histones ◽  
Heterochromatin Assembly

Although the Ran GTPase-activating protein RanGAP mainly functions in the cytoplasm, several lines of evidence indicate a nuclear function of RanGAP. We found that Schizosaccharomyces pombe RanGAP, SpRna1, bound the core of histone H3 (H3) and enhanced Clr4-mediated H3-lysine 9 (K9) methylation. This enhancement was not observed for methylation of the H3-tail containing K9 and was independent of SpRna1–RanGAP activity, suggesting that SpRna1 itself enhances Clr4-mediated H3-K9 methylation via H3. Although most SpRna1 is in the cytoplasm, some cofractionated with H3. Sprna1ts mutations caused decreases in Swi6 localization and H3-K9 methylation at all three heterochromatic regions of S. pombe. Thus, nuclear SpRna1 seems to be involved in heterochromatin assembly. All core histones bound SpRna1 and inhibited SpRna1–RanGAP activity. In contrast, Clr4 abolished the inhibitory effect of H3 on the RanGAP activity of SpRna1 but partially affected the other histones. SpRna1 formed a trimeric complex with H3 and Clr4, suggesting that nuclear SpRna1 is reciprocally regulated by histones, especially H3, and Clr4 on the chromatin to function for higher order chromatin assembly. We also found that SpRna1 formed a stable complex with Xpo1/Crm1 plus Ran-GTP, in the presence of H3.

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