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  • Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose).

Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose).

Nature communications (2021-03-03)
Kengo Watanabe, Kazuhiro Morishita, Xiangyu Zhou, Shigeru Shiizaki, Yasuo Uchiyama, Masato Koike, Isao Naguro, Hidenori Ichijo
ABSTRACT

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 inactivation. 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.

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Roche
Poly(A), lyophilized, suitable for PCR, pkg of 100 mg
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100 μg
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