The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity

P. Doñate-Macián, J. Jungfleisch, G. Pérez-Vilaró, F. Rubio-Moscardo, A. Perálvarez-Marín, J. Diez, M. A. Valverde

Research output: Contribution to journalArticleResearch

40 Citations (Scopus)


© 2018 The Author(s). Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity.
Original languageEnglish
Article number2307
JournalNature Communications
Publication statusPublished - 1 Dec 2018


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