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TRPP2 channels regulate apoptosis through the Ca 2+ concentration in the endoplasmic reticulum
Author(s) -
Wegierski Tomasz,
Steffl Daniel,
Kopp Christoph,
Tauber Robert,
Buchholz Björn,
Nitschke Roland,
Kuehn E Wolfgang,
Walz Gerd,
Köttgen Michael
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.307
Subject(s) - endoplasmic reticulum , biology , apoptosis , microbiology and biotechnology , biochemistry
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.

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