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Wegierski T
,
Steffl D
,
Kopp C
,
Tauber R
,
Buchholz B
,
Nitschke R
,
Kuehn EW
,
Walz G
,
Köttgen M
.
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Ca(2+) is an important signalling molecule that regulates multiple cellular processes, including apoptosis. Although Ca(2+) influx through transient receptor potential (TRP) channels in the plasma membrane is known to trigger cell death, the function of intracellular TRP proteins in the regulation of Ca(2+)-dependent signalling pathways and apoptosis has remained elusive. Here, we show that TRPP2, the ion channel mutated in autosomal dominant polycystic kidney disease (ADPKD), protects cells from apoptosis by lowering the Ca(2+) concentration in the endoplasmic reticulum (ER). ER-resident TRPP2 counteracts the activity of the sarcoendoplasmic Ca(2+) ATPase by increasing the ER Ca(2+) permeability. This results in diminished cytosolic and mitochondrial Ca(2+) signals upon stimulation of inositol 1,4,5-trisphosphate receptors and reduces Ca(2+) release from the ER in response to apoptotic stimuli. Conversely, knockdown of TRPP2 in renal epithelial cells increases ER Ca(2+) release and augments sensitivity to apoptosis. Our findings indicate an important function of ER-resident TRPP2 in the modulation of intracellular Ca(2+) signalling, and provide a molecular mechanism for the increased apoptosis rates in ADPKD upon loss of TRPP2 channel function.
Arnaudeau,
Calreticulin differentially modulates calcium uptake and release in the endoplasmic reticulum and mitochondria.
2002, Pubmed
Arnaudeau,
Calreticulin differentially modulates calcium uptake and release in the endoplasmic reticulum and mitochondria.
2002,
Pubmed
Arnaudeau,
Mitochondria recycle Ca(2+) to the endoplasmic reticulum and prevent the depletion of neighboring endoplasmic reticulum regions.
2001,
Pubmed
Berridge,
The versatility and universality of calcium signalling.
2000,
Pubmed
Boca,
Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway.
2006,
Pubmed
Boletta,
Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells.
2000,
Pubmed
Boletta,
Role of polycystins in renal tubulogenesis.
2003,
Pubmed
Bukanov,
Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine.
2006,
Pubmed
Cai,
Identification and characterization of polycystin-2, the PKD2 gene product.
1999,
Pubmed
Chen,
Transport function of the naturally occurring pathogenic polycystin-2 mutant, R742X.
2001,
Pubmed
,
Xenbase
Demaurex,
Cell biology. Apoptosis--the calcium connection.
2003,
Pubmed
Ecder,
Caspases, Bcl-2 proteins and apoptosis in autosomal-dominant polycystic kidney disease.
2002,
Pubmed
Foyouzi-Youssefi,
Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum.
2000,
Pubmed
Grynkiewicz,
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
1985,
Pubmed
Hidaka,
PIGEA-14, a novel coiled-coil protein affecting the intracellular distribution of polycystin-2.
2004,
Pubmed
Hofer,
Capacitative Ca2+ entry is closely linked to the filling state of internal Ca2+ stores: a study using simultaneous measurements of ICRAC and intraluminal [Ca2+].
1998,
Pubmed
Høyer-Hansen,
Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2.
2007,
Pubmed
Jentsch,
Ion channels: function unravelled by dysfunction.
2004,
Pubmed
Kip,
[Ca2+]i reduction increases cellular proliferation and apoptosis in vascular smooth muscle cells: relevance to the ADPKD phenotype.
2005,
Pubmed
Köttgen,
TRPP2 and autosomal dominant polycystic kidney disease.
2007,
Pubmed
Köttgen,
P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport.
2003,
Pubmed
,
Xenbase
Köttgen,
Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation.
2005,
Pubmed
Köttgen,
Subcellular localization and trafficking of polycystins.
2005,
Pubmed
Koulen,
Polycystin-2 is an intracellular calcium release channel.
2002,
Pubmed
Li,
Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling.
2005,
Pubmed
,
Xenbase
Lin,
Bcl-2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation.
1999,
Pubmed
Miller,
The role of TRP channels in oxidative stress-induced cell death.
2006,
Pubmed
Miyawaki,
Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin.
1997,
Pubmed
Mochizuki,
PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein.
1996,
Pubmed
Montell,
The TRP superfamily of cation channels.
2005,
Pubmed
Moser,
Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.
1997,
Pubmed
Nakamura,
Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis.
2000,
Pubmed
Nilius,
Transient receptor potential cation channels in disease.
2007,
Pubmed
Orrenius,
Regulation of cell death: the calcium-apoptosis link.
2003,
Pubmed
Pinton,
Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in Bcl-2-overexpressing cells.
2000,
Pubmed
Pinton,
Bcl-2 and Ca2+ homeostasis in the endoplasmic reticulum.
2006,
Pubmed
Pinton,
The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action.
2001,
Pubmed
Piontek,
A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1.
2007,
Pubmed
Rizzuto,
Calcium and apoptosis: facts and hypotheses.
2003,
Pubmed
Rizzuto,
Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.
1998,
Pubmed
Scorrano,
BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis.
2003,
Pubmed
Starremans,
A mouse model for polycystic kidney disease through a somatic in-frame deletion in the 5' end of Pkd1.
2008,
Pubmed
Szalai,
Apoptosis driven by IP(3)-linked mitochondrial calcium signals.
1999,
Pubmed
Tao,
Caspase-3 gene deletion prolongs survival in polycystic kidney disease.
2008,
Pubmed
Tao,
Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease.
2005,
Pubmed
Trudel,
C-myc-induced apoptosis in polycystic kidney disease is Bcl-2 and p53 independent.
1997,
Pubmed
Veis,
Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair.
1993,
Pubmed
Walz,
Therapeutic approaches in autosomal dominant polycystic kidney disease (ADPKD): is there light at the end of the tunnel?
2006,
Pubmed
Wiznerowicz,
Conditional suppression of cellular genes: lentivirus vector-mediated drug-inducible RNA interference.
2003,
Pubmed
Woo,
Apoptosis and loss of renal tissue in polycystic kidney diseases.
1995,
Pubmed
