TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells

被引：16

作者：

Arhatte, Malika ^{[1
]}

Gunaratne, Gihan S. ^{[2
]}

El Boustany, Charbel ^{[1
]}

Kuo, Ivana Y. ^{[3
]}

Moro, Celine ^{[1
]}

Duprat, Fabrice ^{[1
]}

Plaisant, Magali ^{[1
]}

Duval, Helene ^{[1
]}

Li, Dahui ^{[4
]}

Picard, Nicolas ^{[5
]}

Couvreux, Anais ^{[1
]}

Duranton, Christophe ^{[6
]}

Rubera, Isabelle ^{[6
]}

Pagnotta, Sophie ^{[7
]}

Lacas-Gervais, Sandra ^{[7
]}

Ehrlich, Barbara E. ^{[8
]}

Marchant, Jonathan S. ^{[9
]}

Savage, Aaron M. ^{[10
,11
]}

van Eeden, Fredericus J. M. ^{[11
,12
]}

Wilkinson, Robert N. ^{[10
,11
]}

Demolombe, Sophie ^{[1
]}

Honore, Eric ^{[1
]}

Patel, Amanda ^{[1
]}

机构：

[1] Univ Cote dAzur, CNRS, INSERM, Inst Pharmacol Mol & Cellulaire,Labex ICST, F-06560 Valbonne, France

[2] Univ Minnesota, Dept Pharmacol, 3-249 Millard Hall, Minneapolis, MN 55455 USA

[3] Loyola Univ Chicago, Stritch Sch Med, Cell & Mol Physiol, Maywood, IL 60153 USA

[4] Univ Hong Kong, Dept Pharmacol & Pharm, State Key Lab Pharmaceut Biotechnol, Hong Kong, Peoples R China

[5] Univ Lyon 1, UMR 5305 CNRS, Lab Tissue Biol & Therapeut Engn, F-69367 Lyon, France

[6] Univ Cote dAzur, LP2M CNRS UMR7370, Labex ICST, Med Fac, F-06108 Nice, France

[7] Univ Cote dAzur, CCMA UFR Sci, F-06108 Nice, France

[8] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

[9] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA

[10] Univ Sheffield, Med Sch, Dept Infect Immun & Cardiovasc Dis, Sheffield S10 2TN, S Yorkshire, England

[11] Univ Sheffield, Bateson Ctr, Sheffield S10 2TN, S Yorkshire, England

[12] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国生物技术与生命科学研究理事会;

关键词：

POLYCYSTIC KIDNEY-DISEASE; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CONTACT SITES; CHANNEL; APOPTOSIS; CA2+; EXPRESSION; AUTOPHAGY; LYSOSOMES;

D O I：

10.1038/s41467-019-10045-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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