A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress.
Cell Rep
; 22(11): 2809-2817, 2018 03 13.
Article
en En
| MEDLINE
| ID: mdl-29539411
ABSTRACT
Cell volume regulation is a vital system for cellular activities. When perturbed by hypoosmotic or hyperosmotic stress, cells immediately induce the cell volume recovery system, regulatory volume decrease (RVD) or regulatory volume increase (RVI), respectively. In contrast to the knowledge about effector molecules, the molecular mechanisms linking osmosensing to RVD/RVI induction remain unknown. Additionally, few reciprocal responders in the bidirectional osmotic stress response have been identified. We previously reported that ASK3 bidirectionally switches its kinase activity under osmotic stress. Herein we demonstrate that ASK3 controls both RVD and RVI under osmotic stress. Using a high-content genome-wide small interfering RNA (siRNA) screen, we identify PP6 as a direct ASK3 inactivator. Furthermore, PP6 rapidly interacts with ASK3 in an osmolality-dependent manner, and it inactivates ASK3 to induce RVI and, thereby, cell survival under hyperosmotic stress. These findings suggest that the PP6-ASK3 interaction is a core module in the bidirectional osmotic stress response.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Presión Osmótica
/
Fosfoproteínas Fosfatasas
/
Osmorregulación
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article