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Phospholipid scrambling induced by an ion channel/metabolite transporter complex

Author

Listed:
  • Han Niu

    (Yoshida-Honmachi
    Yoshida)

  • Masahiro Maruoka

    (Yoshida-Honmachi
    Institute for Biomedical Sciences)

  • Yuki Noguchi

    (Yoshida-Honmachi)

  • Hidetaka Kosako

    (Tokushima University)

  • Jun Suzuki

    (Yoshida-Honmachi
    Yoshida
    Institute for Biomedical Sciences
    Kawaguchi)

Abstract

Cells establish the asymmetrical distribution of phospholipids and alter their distribution by phospholipid scrambling (PLS) to adapt to environmental changes. Here, we demonstrate that a protein complex, consisting of the ion channel Tmem63b and the thiamine transporter Slc19a2, induces PLS upon calcium (Ca2+) stimulation. Through revival screening using a CRISPR sgRNA library on high PLS cells, we identify Tmem63b as a PLS-inducing factor. Ca2+ stimulation-mediated PLS is suppressed by deletion of Tmem63b, while human disease-related Tmem63b mutants induce constitutive PLS. To search for a molecular link between Ca2+ stimulation and PLS, we perform revival screening on Tmem63b-overexpressing cells, and identify Slc19a2 and the Ca2+-activated K+ channel Kcnn4 as PLS-regulating factors. Deletion of either of these genes decreases PLS activity. Biochemical screening indicates that Tmem63b and Slc19a2 form a heterodimer. These results demonstrate that a Tmem63b/Slc19a2 heterodimer induces PLS upon Ca2+ stimulation, along with Kcnn4 activation.

Suggested Citation

  • Han Niu & Masahiro Maruoka & Yuki Noguchi & Hidetaka Kosako & Jun Suzuki, 2024. "Phospholipid scrambling induced by an ion channel/metabolite transporter complex," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51939-w
    DOI: 10.1038/s41467-024-51939-w
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    References listed on IDEAS

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