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Downregulation of KCNQ4 by Janus Kinase 2

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Abstract

Janus kinase-2 (JAK2) participates in the signaling of several hormones, growth factors and cytokines. Further stimulators of JAK2 include osmotic cell shrinkage, and the kinase activates the cell volume regulatory Na+/H+ exchanger. The kinase may thus participate in cell volume regulation. Cell shrinkage is known to inhibit K+ channels. Volume-regulatory K+ channels include the voltage-gated K+ channel KCNQ4. The present study explored the effect of JAK2 on KCNQ4 channel activity. KCNQ4 was expressed in Xenopus oocytes with or without wild-type JAK2, constitutively active V617FJAK2 or inactive K882EJAK2; and cell membrane conductance was determined by dual-electrode voltage clamp. Expression of KCNQ4 was followed by the appearance of voltage-gated K+ conductance. Coexpression of JAK2 or of V617FJAK2, but not of K882EJAK2, resulted in a significant decrease in conductance. Treatment of KCNQ4 and JAK2 coexpressing oocytes with the JAK2 inhibitor AG490 (40 μM) was followed by an increase in conductance. Treatment of KCNQ4 expressing oocytes with brefeldin A (5 μM) was followed by a decrease in conductance, which was similar in oocytes expressing KCNQ4 together with JAK2 as in oocytes expressing KCNQ4 alone. Thus, JAK2 apparently does not accelerate channel protein retrieval from the cell membrane. In conclusion, JAK2 downregulates KCNQ4 activity and thus counteracts K+ exit, an effect which may contribute to cell volume regulation.

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Acknowledgment

The authors acknowledge the meticulous preparation of the manuscript by Lejla Subasic and Sari Rübe and technical support by Elfriede Faber. This study was supported by the Deutsche Forschungsgemeinschaft (GRK 1302, SFB 773 B4/A1, La 315/13-3).

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Authors and Affiliations

  1. Department of Physiology I, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany

    Zohreh Hosseinzadeh, Mentor Sopjani, Tatsiana Pakladok, Shefalee K. Bhavsar & Florian Lang

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  1. Zohreh Hosseinzadeh
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  2. Mentor Sopjani
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  3. Tatsiana Pakladok
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  4. Shefalee K. Bhavsar
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  5. Florian Lang
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Correspondence to Florian Lang.

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The first two authors contributed equally and thus share first authorship.

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Hosseinzadeh, Z., Sopjani, M., Pakladok, T. et al. Downregulation of KCNQ4 by Janus Kinase 2. J Membrane Biol 246, 335–341 (2013). https://doi.org/10.1007/s00232-013-9537-8

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  • DOI: https://doi.org/10.1007/s00232-013-9537-8

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