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TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

Author

Listed:
  • Malika Arhatte

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Gihan S. Gunaratne

    (University of Minnesota)

  • Charbel El Boustany

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Ivana Y. Kuo

    (Cell and Molecular Physiology Stritch School of Medicine Loyola University Chicago)

  • Céline Moro

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Fabrice Duprat

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Magali Plaisant

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Hélène Duval

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Dahui Li

    (The University of Hong Kong)

  • Nicolas Picard

    (Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305 CNRS, University Lyon 1)

  • Anais Couvreux

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Christophe Duranton

    (Université Côte d’Azur, LP2M CNRS-UMR7370, Labex ICST, Medical Faculty)

  • Isabelle Rubera

    (Université Côte d’Azur, LP2M CNRS-UMR7370, Labex ICST, Medical Faculty)

  • Sophie Pagnotta

    (Université Côte d’Azur)

  • Sandra Lacas-Gervais

    (Université Côte d’Azur)

  • Barbara E. Ehrlich

    (Yale University)

  • Jonathan S. Marchant

    (Medical College of Wisconsin)

  • Aaron M. Savage

    (University of Sheffield
    University of Sheffield)

  • Fredericus J. M. Eeden

    (University of Sheffield
    University of Sheffield)

  • Robert N. Wilkinson

    (University of Sheffield
    University of Sheffield)

  • Sophie Demolombe

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Eric Honoré

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Amanda Patel

    (Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

Abstract

Mutations in the polycystins cause autosomal dominant polycystic kidney disease (ADPKD). Here we show that transmembrane protein 33 (TMEM33) interacts with the ion channel polycystin-2 (PC2) at the endoplasmic reticulum (ER) membrane, enhancing its opening over the whole physiological calcium range in ER liposomes fused to planar bilayers. Consequently, TMEM33 reduces intracellular calcium content in a PC2-dependent manner, impairs lysosomal calcium refilling, causes cathepsins translocation, inhibition of autophagic flux upon ER stress, as well as sensitization to apoptosis. Invalidation of TMEM33 in the mouse exerts a potent protection against renal ER stress. By contrast, TMEM33 does not influence pkd2-dependent renal cystogenesis in the zebrafish. Together, our results identify a key role for TMEM33 in the regulation of intracellular calcium homeostasis of renal proximal convoluted tubule cells and establish a causal link between TMEM33 and acute kidney injury.

Suggested Citation

  • Malika Arhatte & Gihan S. Gunaratne & Charbel El Boustany & Ivana Y. Kuo & Céline Moro & Fabrice Duprat & Magali Plaisant & Hélène Duval & Dahui Li & Nicolas Picard & Anais Couvreux & Christophe Duran, 2019. "TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10045-y
    DOI: 10.1038/s41467-019-10045-y
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