Skip to Main content Skip to Navigation
Journal articles

TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

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 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.
Complete list of metadatas
Contributor : Nicolas Picard <>
Submitted on : Tuesday, January 12, 2021 - 9:25:10 PM
Last modification on : Thursday, January 14, 2021 - 3:11:29 AM


Publisher files allowed on an open archive



Malika Arhatte, Gihan Gunaratne, Charbel El Boustany, Ivana Kuo, Céline Moro, et al.. TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Nature Communications, Nature Publishing Group, 2019, 10, pp.2024. ⟨10.1038/s41467-019-10045-y⟩. ⟨hal-02322062⟩



Record views


Files downloads