PUBLICATION
TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells
- Authors
- Arhatte, M., Gunaratne, G.S., El Boustany, C., Kuo, I.Y., Moro, C., Duprat, F., Plaisant, M., Duval, H., Li, D., Picard, N., Couvreux, A., Duranton, C., Rubera, I., Pagnotta, S., Lacas-Gervais, S., Ehrlich, B.E., Marchant, J.S., Savage, A.M., van Eeden, F.J.M., Wilkinson, R.N., Demolombe, S., Honoré, E., Patel, A.
- ID
- ZDB-PUB-190507-19
- Date
- 2019
- Source
- Nature communications 10: 2024 (Journal)
- Registered Authors
- Wilkinson, Robert
- Keywords
- none
- MeSH Terms
-
- Acute Kidney Injury/genetics
- Acute Kidney Injury/pathology*
- Animals
- Calcium/metabolism*
- Cell Membrane/metabolism
- Disease Models, Animal
- Embryo, Nonmammalian
- Endoplasmic Reticulum/metabolism
- Endoplasmic Reticulum Stress
- Epithelial Cells/cytology
- Epithelial Cells/metabolism
- Gene Knockdown Techniques
- HeLa Cells
- Humans
- Kidney Tubules, Proximal/cytology
- Kidney Tubules, Proximal/metabolism*
- Lysosomes/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Membrane Proteins/physiology
- Mice
- Mice, Knockout
- Mutation
- Polycystic Kidney, Autosomal Dominant/genetics
- Polycystic Kidney, Autosomal Dominant/pathology
- RNA, Small Interfering/metabolism
- TRPP Cation Channels/genetics
- TRPP Cation Channels/metabolism*
- TRPP Cation Channels/physiology
- Zebrafish
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology
- PubMed
- 31048699 Full text @ Nat. Commun.
Citation
Arhatte, M., Gunaratne, G.S., El Boustany, C., Kuo, I.Y., Moro, C., Duprat, F., Plaisant, M., Duval, H., Li, D., Picard, N., Couvreux, A., Duranton, C., Rubera, I., Pagnotta, S., Lacas-Gervais, S., Ehrlich, B.E., Marchant, J.S., Savage, A.M., van Eeden, F.J.M., Wilkinson, R.N., Demolombe, S., Honoré, E., Patel, A. (2019) TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Nature communications. 10:2024.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping