Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration

Autor: Kristin Seltmann, Britta Hettich, Seraina Abele, Selina Gurri, Valeria Mantella, Jean‐Christophe Leroux, Sabine Werner
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 13, Iss 4, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12430
Popis: Abstract 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 β‐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.
Databáze: Directory of Open Access Journals
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