Direct ionic stress sensing and mitigation by the transcription factor NFAT5

• DOI: 10.1101/2023.09.23.559074
• Publication Date: 2023-09-24T08:45:16Z
• Authors: Chandni B. Khandwala; Parijat Sarkar; H. Broder Schmidt; Mengxiao Ma; Maia Kinnebrew; Ganesh V. Pusapati; Bhaven B. Patel; Desiree Tillo; Andres M. Lebensohn; Rajat Rohatgi
• Keywords: Transcription

SUMMARY Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense enable adaptation to stress remain poorly understood in animals. We find the transcription factor NFAT5 directly senses solution using a C-terminal intrinsically disordered region. Both intact cells purified system, forms dynamic, reversible biomolecular condensates response increasing strength. This self-associative property, conserved from insects mammals, allows accumulate nucleus activate genes restore cellular ion content. Mutations reduce condensation or those promote aggregation both activity, highlighting importance optimally tuned associative interactions. Remarkably, human alone sufficient reconstitute mammalian transcriptional hypertonic yeast. Thus sensor effector cell-autonomous pathway animal cells.