RT Journal Article
SR Electronic
T1 Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.20.049759
DO 10.1101/2020.04.20.049759
A1 Kengo Watanabe
A1 Kazuhiro Morishita
A1 Xiangyu Zhou
A1 Shigeru Shiizaki
A1 Yasuo Uchiyama
A1 Masato Koike
A1 Isao Naguro
A1 Hidenori Ichijo
YR 2020
UL http://biorxiv.org/content/early/2020/04/20/2020.04.20.049759.abstract
AB Cells are under threat of osmotic perturbation; and 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 report that macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inactivation. A genome-wide small interfering RNA (siRNA) screen identified 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.Competing Interest StatementThe authors have declared no competing interest.