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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

TRPP2 channels regulate apoptosis through the Ca2+ concentration in the endoplasmic reticulum

Tomasz Wegierski1, Daniel Steffl, Christoph Kopp

  • 1Renal Division, University Hospital of Freiburg, Freiburg, Germany.

The EMBO Journal
|January 21, 2009
PubMed

Insights

Transient Receptor Potential PolyCystic 2 (TRPP2) channels in the endoplasmic reticulum protect cells from apoptosis. Loss of TRPP2 function increases cell death, offering insights into autosomal dominant polycystic kidney disease.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Calcium ions (Ca2+) are crucial signaling molecules regulating cellular processes like apoptosis.
  • While plasma membrane Transient Receptor Potential (TRP) channels mediate Ca2+ influx and cell death, the role of intracellular TRP channels in apoptosis remains unclear.

Purpose of the Study:

  • To investigate the function of intracellular TRP channels, specifically TRPP2, in regulating Ca2+-dependent signaling and apoptosis.
  • To elucidate the role of ER-resident TRPP2 in cellular Ca2+ homeostasis and its implications in autosomal dominant polycystic kidney disease (ADPKD).

Main Methods:

  • Investigated the localization and function of TRPP2 within the endoplasmic reticulum (ER).
  • Assessed the impact of TRPP2 on ER Ca2+ permeability and its counteraction of sarcoendoplasmic Ca2+ ATPase activity.
  • Analyzed cytosolic and mitochondrial Ca2+ signals upon stimulation of inositol 1,4,5-trisphosphate receptors.
  • Examined the effect of TRPP2 knockdown on ER Ca2+ release and apoptosis sensitivity in renal epithelial cells.

Main Results:

  • ER-resident TRPP2 lowers ER Ca2+ concentration by increasing ER Ca2+ permeability, counteracting Ca2+ ATPase activity.
  • TRPP2 activity diminishes cytosolic and mitochondrial Ca2+ signals, reducing ER Ca2+ release during apoptosis.
  • TRPP2 knockdown in renal cells enhances ER Ca2+ release and increases apoptosis sensitivity.

Conclusions:

  • ER-resident TRPP2 plays a significant role in modulating intracellular Ca2+ signaling pathways.
  • TRPP2's function in maintaining ER Ca2+ homeostasis provides a molecular mechanism for increased apoptosis in ADPKD patients with TRPP2 mutations.

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