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TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Nat Commun 2019 05 02;10(1):2024



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85065183745   1 Citation


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.

Author List

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


Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Cell Membrane
Disease Models, Animal
Embryo, Nonmammalian
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Epithelial Cells
Gene Knockdown Techniques
HeLa Cells
Kidney Tubules, Proximal
Membrane Proteins
Mice, Knockout
Polycystic Kidney, Autosomal Dominant
RNA, Small Interfering
TRPP Cation Channels
Zebrafish Proteins
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a