TY - JOUR
T1 - The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity
AU - Doñate-Macián, P.
AU - Jungfleisch, J.
AU - Pérez-Vilaró, G.
AU - Rubio-Moscardo, F.
AU - Perálvarez-Marín, A.
AU - Diez, J.
AU - Valverde, M. A.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - © 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.
AB - © 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.
U2 - 10.1038/s41467-018-04776-7
DO - 10.1038/s41467-018-04776-7
M3 - Article
C2 - 29899501
VL - 9
M1 - 2307
ER -
