Title:
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The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity
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Author:
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Doñate-Macian, Pablo; Jungfleisch, J.; Pérez-Vilaró, Gemma; Rubio-Moscardo, F.; Peralvarez-Marin, Alex; Diez, J.; Valverde, M. A.
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Abstract:
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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. |
Publication date:
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2022-12-12 |
Subject(s):
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-Ion channel signalling -Viral infection |
Rights:
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open access
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https://creativecommons.org/licenses/by/4.0/ |
Document type:
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Article |
Published by:
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Share:
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Uri:
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https://ddd.uab.cat/record/253559
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