TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells.
Acute Kidney Injury
/ genetics
Animals
Calcium
/ metabolism
Cell Membrane
/ metabolism
Disease Models, Animal
Embryo, Nonmammalian
Endoplasmic Reticulum
/ metabolism
Endoplasmic Reticulum Stress
Epithelial Cells
/ cytology
Gene Knockdown Techniques
HeLa Cells
Humans
Kidney Tubules, Proximal
/ cytology
Lysosomes
/ metabolism
Membrane Proteins
/ genetics
Mice
Mice, Knockout
Mutation
Polycystic Kidney, Autosomal Dominant
/ genetics
RNA, Small Interfering
/ metabolism
TRPP Cation Channels
/ genetics
Zebrafish
Zebrafish Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 05 2019
02 05 2019
Historique:
received:
08
08
2018
accepted:
16
04
2019
entrez:
4
5
2019
pubmed:
3
5
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31048699
doi: 10.1038/s41467-019-10045-y
pii: 10.1038/s41467-019-10045-y
pmc: PMC6497644
doi:
Substances chimiques
Membrane Proteins
0
PKD2 protein, zebrafish
0
RNA, Small Interfering
0
TRPP Cation Channels
0
Tmem33 protein, mouse
0
Zebrafish Proteins
0
polycystic kidney disease 2 protein
0
tmem33 protein, zebrafish
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2024Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM088790
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIH HHS
ID : UM1 OD023221
Pays : United States
Références
Cell. 2019 Jan 10;176(1-2):11-42
pubmed: 30633901
Nat Struct Mol Biol. 2017 Feb;24(2):114-122
pubmed: 27991905
J Biol Chem. 2007 Dec 14;282(50):36692-703
pubmed: 17947235
Kidney Int. 2011 Mar;79(6):613-623
pubmed: 21150875
Nat Commun. 2019 Feb 13;10(1):732
pubmed: 30760708
Mol Cell. 2007 Jan 26;25(2):193-205
pubmed: 17244528
J Cell Biol. 2008 Aug 11;182(3):437-47
pubmed: 18695040
Mol Biol Cell. 2013 Apr;24(7):1030-40
pubmed: 23389631
Biomark Med. 2010 Apr;4(2):265-80
pubmed: 20406069
Curr Opin Obstet Gynecol. 2017 Apr;29(2):85-94
pubmed: 28151755
Mol Biol Cell. 2014 Oct 1;25(19):2970-83
pubmed: 25103238
Oncotarget. 2017 Jul 5;8(34):55984-55997
pubmed: 28915568
Development. 2004 Aug;131(16):4085-93
pubmed: 15269167
Cell. 2014 Nov 20;159(5):1027-1041
pubmed: 25416943
PLoS One. 2014 Oct 22;9(10):e111275
pubmed: 25337829
J Biol Chem. 2006 Oct 6;281(40):30299-304
pubmed: 16901900
FASEB J. 2014 May;28(5):2332-46
pubmed: 24558196
Am J Physiol Renal Physiol. 2017 Jan 1;312(1):F96-F108
pubmed: 27760766
J Biol Chem. 2004 May 7;279(19):19987-95
pubmed: 14742446
Toxicol Lett. 2008 Oct 1;181(3):196-204
pubmed: 18789614
J Am Soc Nephrol. 2017 Jan;28(1):209-217
pubmed: 27335120
Genes Dev. 1998 Apr 1;12(7):982-95
pubmed: 9531536
Neuron. 2000 Jan;25(1):177-90
pubmed: 10707982
Nat Genet. 2000 Jan;24(1):75-8
pubmed: 10615132
PLoS One. 2015 Dec 21;10(12):e0145458
pubmed: 26691022
J Cell Sci. 2013 Jan 1;126(Pt 1):289-300
pubmed: 23097044
J Clin Invest. 2007 Aug;117(8):2095-104
pubmed: 17671649
J Mol Cell Cardiol. 2018 May;118:110-121
pubmed: 29518398
Development. 2009 Sep;136(17):2883-92
pubmed: 19666820
Eur J Biochem. 1983 Dec 15;137(3):391-7
pubmed: 6319122
Cell. 2016 Oct 20;167(3):763-773.e11
pubmed: 27768895
Am J Physiol Renal Physiol. 2015 Feb 1;308(3):F267-74
pubmed: 25428129
Curr Biol. 2010 Jun 8;20(11):1029-34
pubmed: 20434336
Kobe J Med Sci. 2014 Nov 06;60(3):E57-65
pubmed: 25612671
Elife. 2018 Feb 14;7:
pubmed: 29443690
Stem Cells. 2018 Apr;36(4):501-513
pubmed: 29271023
Nat Cell Biol. 2002 Mar;4(3):191-7
pubmed: 11854751
Cell Rep. 2018 Dec 11;25(11):3180-3193.e7
pubmed: 30540949
J Am Soc Nephrol. 2002 Jul;13(7):1855-64
pubmed: 12089381
Cell Rep. 2012 Mar 29;1(3):241-50
pubmed: 22832196
J Biol Chem. 2009 Dec 25;284(52):36431-41
pubmed: 19854836
Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F740-F751
pubmed: 27488998
Sci Rep. 2016 Jun 07;6:27112
pubmed: 27271556
Cell Death Differ. 2007 Sep;14(9):1576-82
pubmed: 17612585
J Biol Chem. 2019 Jan 18;294(3):772-782
pubmed: 30429217
J Cell Sci. 2015 Jan 15;128(2):305-16
pubmed: 25413348
J Clin Invest. 2014 Jun;124(6):2315-24
pubmed: 24892705
Mol Cell Biol. 2003 Jan;23(2):665-76
pubmed: 12509464
Nephrol Dial Transplant. 2002 Dec;17(12):2138-44
pubmed: 12454224
Am J Pathol. 2009 Oct;175(4):1493-503
pubmed: 19729489
Science. 1996 May 31;272(5266):1339-42
pubmed: 8650545
Nat Cell Biol. 2016 Jun;18(6):657-67
pubmed: 27214279
Int J Mol Sci. 2017 Aug 28;18(9):
pubmed: 28846632
Elife. 2016 May 23;5:
pubmed: 27213518
J Cell Biol. 2010 May 31;189(5):795-811
pubmed: 20498018
Mol Cell Biol. 2006 Dec;26(24):9220-31
pubmed: 17030611
Am J Physiol. 1999 Jul;277(1):F17-25
pubmed: 10409293
Front Cell Dev Biol. 2017 Dec 19;5:114
pubmed: 29312937
Breast Cancer Res Treat. 2015 Sep;153(2):285-97
pubmed: 26268696
J Biol Chem. 2010 Jun 11;285(24):18794-805
pubmed: 20375013
J Biol Chem. 2012 May 18;287(21):17232-40
pubmed: 22474326
EMBO J. 2009 Mar 4;28(5):490-9
pubmed: 19153608
Proc Natl Acad Sci U S A. 2010 May 18;107(20):9176-81
pubmed: 20439752
Cell. 2009 Oct 30;139(3):587-96
pubmed: 19879844