The molecular mechanism for ionic stress sensing and adaptation in mammalian cells
Abstract/Contents
- Abstract
- Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. Remarkably, human NFAT5 alone is sufficient to reconstitute a mammalian transcriptional response to ionic or hypertonic stress in yeast. Thus NFAT5 is both the sensor and effector of a cell-autonomous ionic stress response pathway in animal cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Patel, Chandni |
|---|---|
| Degree supervisor | Rohatgi, Rajat |
| Thesis advisor | Rohatgi, Rajat |
| Thesis advisor | Brandman, Onn |
| Thesis advisor | Harbury, Pehr |
| Thesis advisor | Krasnow, Mark, 1956- |
| Degree committee member | Brandman, Onn |
| Degree committee member | Harbury, Pehr |
| Degree committee member | Krasnow, Mark, 1956- |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Chandni Patel. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/bk861qw6664 |
Access conditions
- Copyright
- © 2023 by Chandni Patel
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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