.png){kind=icon}
.png){kind=icon}
Return
Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration
.png){kind=icon}
OA
AI
DOI：10.1002/jev2.12430.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Chloride channel accessory 2 (CLCA2) is a transmembrane protein, which promotes adhesion of keratinocytes and their survival in response to hyperosmotic stress. Here we show that CLCA2 is transported to the nucleus of keratinocytes via extracellular vesicles. The nuclear localization is functionally relevant, since wild-type CLCA2, but not a mutant lacking the nuclear localization signal, suppressed migration of keratinocytes and protected them from hyperosmotic stress-induced cell death. In the nucleus, CLCA2 bound to and activated beta-catenin, resulting in enhanced expression of Wnt target genes. Mass-spectrometry-based interaction screening and functional rescue studies identified RNA binding protein 3 as a key effector of nuclear CLCA2. This is of likely relevance in vivo because both proteins co-localize in the human epidermis. Together, these results identify an unexpected nuclear function of CLCA2 in keratinocytes under homeostatic and stress conditions and suggest a role of extracellular vesicles and their nuclear transport in the control of key cellular activities.
Keywords:
cell death
CLCA2
extracellular vesicles
hyperosmotic stress
keratinocytes
migration
nuclear transport
RBM3
beta-catenin
Journal
IF:
14.5
Papers:
1.1K
Citations:
1.5W