TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Journal Article

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Authors: Arhatte, M; Gunaratne, GS; El Boustany, C; Kuo, IY; Moro, C; Duprat, F; Plaisant, M; Duval, H; Li, D; Picard, N; Couvreux, A; Duranton, C; Rubera, I; Pagnotta, S; Lacas-Gervais, S; Ehrlich, BE; Marchant, JS; Savage, AM; van Eeden, FJM; Wilkinson, RN; Demolombe, S; Honoré, E; Patel, A
Article Title: 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 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.
Journal Title: Nature communications
ISSN: 2041-1723; 2041-1723
Publisher: Unknown  
Date Published: 2019