TY - JOUR AU - AB - ARTICLE https://doi.org/10.1038/s41467-021-21614-5 OPEN Cells recognize osmotic stress through liquid–liquid phase separation lubricated with poly(ADP-ribose) 1 1 1 1 2 Kengo Watanabe , Kazuhiro Morishita , Xiangyu Zhou , Shigeru Shiizaki , Yasuo Uchiyama , 3 1 1 Masato Koike , Isao Naguro & Hidenori Ichijo Cells are under threat of osmotic perturbation; cell volume maintenance is critical in cerebral edema, inflammation and aging, in which prominent changes in intracellular or extracellular osmolality emerge. After osmotic stress-enforced cell swelling or shrinkage, the cells regulate intracellular osmolality to recover their volume. However, the mechanisms recognizing osmotic stress remain obscured. We previously clarified that apoptosis signal-regulating kinase 3 (ASK3) bidirectionally responds to osmotic stress and regulates cell volume recovery. Here, we show that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inacti- vation. A genome-wide small interfering RNA (siRNA) screen identifies an ASK3 inactivation regulator, nicotinamide phosphoribosyltransferase (NAMPT), related to poly(ADP-ribose) signaling. Furthermore, we clarify that poly(ADP-ribose) keeps ASK3 condensates in the liquid phase and enables ASK3 to become inactivated under hyperosmotic stress. Our findings demonstrate that cells rationally incorporate physicochemical phase separation into their osmosensing systems. 1 2 Laboratory of Cell Signaling, Graduate TI - Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose) DO - 10.1101/2020.04.20.049759 DA - 2020-04-20 UR - https://www.deepdyve.com/lp/unpaywall/cells-recognize-osmotic-stress-through-liquid-liquid-phase-separation-5I7SeerYNi DP - DeepDyve ER -