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

Doñate-Macián, Pau; Jungfleisch, Jennifer, 1986-; Pérez Vilaró, Gemma, 1985-; Rubio Moscardó, Fanny; Perálvarez Marín, Alex; Díez Antón, Juana, 1962-; Valverde, M. A. (Miguel Ángel), 1963-

doi:http://dx.doi.org/10.1038/s41467-018-04776-7

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

Llicència

Citació

Doñate-Macián P, Jungfleisch J, Pérez-Vilaró G, Rubio-Moscardo F, Perálvarez-Marín A, Diez J et al. The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity. Nat Commun. 2018 Jun 13;9(1):2307. DOI: 10.1038/s41467-018-04776-7

Resum

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.