Inter-Cellular Transport of Ran GTPase

Khuperkar, Deepak; Helen, Mary; Magre, Indrasen; Joseph, Jomon

doi:10.1371/journal.pone.0125506

Cited by 14 publications

(9 citation statements)

References 62 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest a mechanism where Ran protein could play a role in microtubule-dependent cellular functions, such as membrane vesicle transport between the intracellular compartments, including the plasma membrane and the nucleus. Moreover, it has been shown that Ran can be secreted and distributed between cells thereby contributing to a localization of Ran to the plasma membrane 44 . Given the ability of Ran to move from cell to cell and its association with microtubules cytoskeleton elements, it is tempting to speculate that an intracellular transport of cargoes loaded with Ran destined for secretion potentially occurs through the export complex.…”

Section: Discussionmentioning

confidence: 99%

Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

et al. 2019

View full text Add to dashboard Cite

Ran is a nucleocytoplasmic shuttle protein that is involved in cell cycle regulation, nuclear-cytoplasmic transport, and cell transformation. Ran plays an important role in cancer cell survival and cancer progression. Here, we show that, in addition to the nucleocytoplasmic localization of Ran, this GTPase is specifically associated with the plasma membrane/ruffles of ovarian cancer cells. Ran depletion has a drastic effect on RhoA stability and inhibits RhoA localization to the plasma membrane/ruffles and RhoA activity. We further demonstrate that the DEDDDL domain of Ran is required for the interaction with serine 188 of RhoA, which prevents RhoA degradation by the proteasome pathway. Moreover, the knockdown of Ran leads to a reduction of ovarian cancer cell invasion by impairing RhoA signalling. Our findings provide advanced insights into the mode of action of the Ran-RhoA signalling axis and may represent a potential therapeutic avenue for drug development to prevent ovarian tumour metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, a number of "artificial Ranactivated mutants" have been developed including RanF35A, RanQ69L, and RanG19V (Ren et al, 1995;Lounsbury et al, 1996;Ly et al, 2010). Using immunofluorescence approaches, it has been reported that while wild-type (WT) Ran was localized predominantly in the nucleus, Ran mutants localized mainly on the NE (Lounsbury et al, 1996;Khuperkar et al, 2015). Interestingly, it was shown that ectopic expression of one of them (RanF35A) is able to transform fibroblast cells, which are then able to form tumors in mice, demonstrating that Ran activation is sufficient for cell transformation and tumor initiation (Ly et al, 2010).…”

Section: Proliferative Signalingmentioning

confidence: 99%

“…Another study has shown that Ran itself, particularly the active form, can be transferred between donor and recipient cells (Khuperkar et al, 2015); however, the mode of action and the consequences of this transfer remain to be elucidated.…”

Section: Activating Invasion and Metastasismentioning

confidence: 99%

Ran GTPase: A Key Player in Tumor Progression and Metastasis

Boudhraa

Carmona

Provencher

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Ran (Ras-related nuclear protein) GTPase is a member of the Ras superfamily. Like all the GTPases, Ran cycles between an active (GTP-bound) and inactive (GDP-bound) state. However, Ran lacks the CAAX motif at its C-terminus, a feature of other small GTPases that ensures a plasma membrane localization, and largely traffics between the nucleus and the cytoplasm. Ran regulates nucleo-cytoplasmic transport of molecules through the nuclear pore complex and controls cell cycle progression through the regulation of microtubule polymerization and mitotic spindle formation. The disruption of Ran expression has been linked to cancer at different levels -from cancer initiation to metastasis. In the present review, we discuss the contribution of Ran in the acquisition of three hallmarks of cancer, namely, proliferative signaling, resistance to apoptosis, and invasion/metastasis, and highlight its prognostic value in cancer patients. In addition, we discuss the use of this GTPase as a therapeutic target in cancer.

show abstract

“…6A , B), suggesting the transcription of ncRNAs to be detrimental in the AG flies. Next, we test the role of RNA transport, which is regulated by RanGTPase [ 47 ]. The result showed that Ran G19V,Q69L or RanRNAi both rescued the AG flies (Fig.…”

Section: Resultsmentioning

confidence: 99%

Increased expression of fragmented tRNA promoted neuronal necrosis

Cao

Xiong

et al. 2021

Cell Death Dis

View full text Add to dashboard Cite

Neuronal necrosis induced by excessive glutamate release is well known to contribute morbidity and mortality in ischemic stroke. Over the past decades, strategies on targeting glutamate receptor did not achieve desirable clinical outcomes. Finding the downstream mechanism of the glutamate receptor activation may provide new targets to suppress the cell death. Previously, our study demonstrated that the increase of H3K4 trimethylation (H3K4me3) played a key detrimental role on neuronal necrosis; however, the mechanism of this histone modification is unclear. Through a genome-wide small RNA sequencing, we identified several tRNA-derived fragments (tRFs) and piwi-interacting RNA (piRNAs) species were enriched in glutamate-induced neuronal necrosis in rat primary neuron cultures, and this enrichment was dependent on the H3K4me3 increase. Strikingly, when we transfected several synthesized tRFs and piRNA species into neurons, the tRFs but not the piRNAs induced neuron swelling and death. The cell death morphology recapitulated neuronal necrosis induced by glutamate. For the cytotoxic effect of tRFs, our data suggested that protein synthesis was inhibited likely through induction of ribosomal stalling. By proteomic analysis of tRFs effect, the most affected pathway was enriched in the mitochondrial metabolism. Consistently, mitochondrial fragmentation was increased in neuronal necrosis, and suppression of mitochondrial fission by genetic manipulation or drug rescued neuronal necrosis. Using our previously established Drosophila model of neuronal necrosis, we found that inhibition of small RNA transcription, blocking RNA transport from nucleus to cytosol, or knocking down Ago1/2 to suppress the RNA interference effect, all rescued the fly death, suggesting transcription and processing of small RNAs contribute to neuronal necrosis. Together, these results indicate that the abnormal transcription of tRFs may play a key role downstream of the H3K4me3 increase. This provides a potential new strategy to suppress neuronal necrosis.

show abstract

Inter-Cellular Transport of Ran GTPase

Cited by 14 publications

References 62 publications

Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

Ran promotes membrane targeting and stabilization of RhoA to orchestrate ovarian cancer cell invasion

Ran GTPase: A Key Player in Tumor Progression and Metastasis

Increased expression of fragmented tRNA promoted neuronal necrosis

Contact Info

Product

Resources

About