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KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis

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  • Ken-ichi Nakajima

    (Institute for Regenerative Cures, School of Medicine, University of California Davis)

  • Kan Zhu

    (Institute for Regenerative Cures, School of Medicine, University of California Davis
    Bioelectromagnetics Laboratory, Zhejiang University School of Medicine)

  • Yao-Hui Sun

    (Institute for Regenerative Cures, School of Medicine, University of California Davis)

  • Bence Hegyi

    (University of California Davis)

  • Qunli Zeng

    (Bioelectromagnetics Laboratory, Zhejiang University School of Medicine)

  • Christopher J. Murphy

    (School of Veterinary Medicine, University of California Davis
    School of Medicine, University of California Davis)

  • J. Victor Small

    (IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences)

  • Ye Chen-Izu

    (University of California Davis)

  • Yoshihiro Izumiya

    (Institute for Regenerative Cures, School of Medicine, University of California Davis
    University of California at Davis)

  • Josef M. Penninger

    (IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences)

  • Min Zhao

    (Institute for Regenerative Cures, School of Medicine, University of California Davis
    School of Medicine, University of California Davis)

Abstract

Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K+ channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine-binding defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents phosphatidylinositol 3,4,5-triphosphate (PIP3) from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields.

Suggested Citation

  • Ken-ichi Nakajima & Kan Zhu & Yao-Hui Sun & Bence Hegyi & Qunli Zeng & Christopher J. Murphy & J. Victor Small & Ye Chen-Izu & Yoshihiro Izumiya & Josef M. Penninger & Min Zhao, 2015. "KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis," Nature Communications, Nature, vol. 6(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9532
    DOI: 10.1038/ncomms9532
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