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TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

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  • Additional Information
    • Contributors:
      Institut de pharmacologie moléculaire et cellulaire (IPMC); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS); University of Minnesota Twin Cities (UMN); University of Minnesota System (UMN); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA); Institut de signalisation, biologie du développement et cancer - Institute of Developmental Biology and Cancer (IBDC); Service d'anatomie et cytologie pathologiques Rennes = Anatomy and Cytopathology Rennes; Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou; Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique (LBTI); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS); Laboratoire de PhysioMédecine Moléculaire (LP2M); Physiologie cellulaire et moléculaire des systèmes intégrés (PCMSI); Centre Commun de Microscopie Appliquée (CCMA); Université Côte d'Azur (UniCA); University Medical Center Carl Gustav Carus, Dresden University of Technology Department of Conserva; ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)
    • Publication Information:
      HAL CCSD
      Nature Publishing Group
    • Publication Date:
      2019
    • Collection:
      HAL Université Côte d'Azur
    • Abstract:
      International audience ; 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 pkd2dependent 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.
    • Accession Number:
      10.1038/s41467-019-10045-y
    • Online Access:
      https://hal.science/hal-02322062
      https://hal.science/hal-02322062v1/document
      https://hal.science/hal-02322062v1/file/s41467-019-10045-y.pdf
      https://doi.org/10.1038/s41467-019-10045-y
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • Accession Number:
      edsbas.BEF3FA05