ArticleMolecular biology of the cell2007
Hyperosmotic stress signaling to the nucleus disrupts the Ran gradient and the production of RanGTP.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 63 citations in OpenAlex.
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- The Nuclear Transporter Importin 13 Can Regulate Stress-Induced Cell Death through the Clusterin/KU70 Axis.Cells · 2023Article
- Lack of Hikeshi activates HSF1 activity under normal conditions and disturbs the heat-shock response.Life science alliance · 2022Article
- Cellular Stress Induces Nucleocytoplasmic Transport Deficits Independent of Stress Granules.Biomedicines · 2022Article
- Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response.Nature communications · 2021Article
- FBW7 couples structural integrity with functional output of primary cilia.Communications biology · 2021Article
- Ubiquitination is essential for recovery of cellular activities after heat shock.Science (New York, N.Y.) · 2021Article
- Local translation in nuclear condensate amyloid bodies.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- TDP-43 Mutation Affects Stress Granule Dynamics in Differentiated NSC-34 Motoneuron-Like Cells.Frontiers in cell and developmental biology · 2021Article
- LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient.PLoS biology · 2020Article
- The RNA-binding protein FUS/TLS undergoes calcium-mediated nuclear egress during excitotoxic stress and is required forThe Journal of biological chemistry · 2019Article
- Fluorescence-based quantification of nucleocytoplasmic transport.Methods (San Diego, Calif.) · 2019Article
- A nuclear lamina-chromatin-Ran GTPase axis modulates nuclear import and DNA damage signaling.Aging cell · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The RanGTP gradient depends on nucleocytoplasmic shuttling of Ran and its nucleotide exchange in the nucleus. Here we show that hyperosmotic stress signaling induced by sorbitol disrupts the Ran protein gradient and reduces the production of RanGTP. Ran gradient disruption is rapid and is followed by early (10-20 min) and late (30-60 min) phases of recovery. Results from SB203580 and siRNA experiments suggest the stress kinase p38 is important for Ran gradient recovery. NTF2 and Mog1, which are transport factors that regulate the nuclear localization of Ran, showed kinetics of delocalization and recovery similar to Ran. Microinjection of a nuclear localization signal reporter protein revealed that sorbitol stress decreases the rate of nuclear import. Sorbitol stress also slowed RCC1 mobility in the nucleus, which is predicted to reduce RCC1 dissociation from chromatin and RanGTP production. This was tested using a FRET biosensor that registers nuclear RanGTP levels, which were reduced in response to sorbitol stress. Although sorbitol alters nucleotide levels, we show that inverting the GTP/GDP ratio in cells is not sufficient to disrupt the Ran gradient. Thus, the Ran system is a target of hyperosmotic stress signaling, and cells use protein localization-based mechanisms as part of a rapid stress response.
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