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Direct ionic stress sensing and mitigation by the transcription factor NFAT5
Chandni B Khandwala1, Parijat Sarkar1, H Broder Schmidt1
1Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Biorxiv : the Preprint Server for Biology
|October 27, 2023
Summary
The transcription factor NFAT5 senses ionic strength by forming condensates, enabling cells to adapt to ionic stress. This mechanism is crucial for maintaining cellular function under osmotic challenges.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Maintaining intracellular ionic strength is vital for cellular functions like protein and genome stability.
- The precise mechanisms by which animal cells sense and respond to ionic stress are not fully understood.
Approach:
- Investigated the role of the transcription factor NFAT5 in sensing ionic strength.
- Utilized intact cells and purified systems to study NFAT5 behavior under varying ionic conditions.
- Examined the impact of mutations on NFAT5 condensation and transcriptional activity.
Key Points:
- NFAT5 directly senses solution ionic strength via its C-terminal intrinsically disordered region.
- NFAT5 forms dynamic, reversible biomolecular condensates in response to increased ionic strength.
- This condensation is conserved across species and is essential for NFAT5's nuclear accumulation and gene activation.
Conclusions:
- NFAT5 acts as both the sensor and effector in a cell-autonomous pathway for ionic stress response.
- Optimally tuned associative interactions of NFAT5 are critical for its function.
- Human NFAT5 can restore a mammalian transcriptional response to ionic stress in yeast, demonstrating its conserved role.
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