Direct ionic stress sensing and mitigation by the transcription factor NFAT5.

Autor:	Khandwala CB; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Sarkar P; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Schmidt HB; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Ma M; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Kinnebrew M; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Pusapati GV; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Patel BB; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Tillo D; Center for Cancer Research Genomics Core, National Cancer Institute, National Institutes of Health, NIH, Building 37, RM 2056B, Bethesda, MD, 20892, USA., Lebensohn AM; Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NIH, Building 37, RM 2056B, Bethesda, MD, 20892, USA., Rohatgi R; Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 24. Date of Electronic Publication: 2023 Sep 24.
DOI:	10.1101/2023.09.23.559074
Abstrakt:	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. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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