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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

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SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce

M Chami1, D Gozuacik, D Lagorce

  • 1The French Institute of Health and Medical Research Institut National de la Santé et de la Recherche Médicale (INSERM/Pasteur U370)/Necker Faculty Institute of Medicine, 75015 Paris, France.

The Journal of Cell Biology
|June 13, 2001
PubMed

Insights

Two novel sarco/endoplasmic reticulum calcium ATPase (SERCA) splice variants (S1Ts) lack calcium-binding ability and form channels that reduce ER calcium, potentially inducing apoptosis in nonmuscle cells.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Sarco/endoplasmic reticulum calcium ATPases (SERCAs) are crucial for regulating intracellular calcium signaling by pumping calcium into the ER.
  • Dysregulation of calcium homeostasis is implicated in various cellular processes and diseases.

Purpose of the Study:

  • To characterize novel SERCA1 splice variants (S1Ts) and elucidate their function in calcium regulation and cellular processes.
  • To investigate the role of S1Ts in nonmuscle cells and their potential involvement in apoptosis.

Main Methods:

  • Semiquantitative RT-PCR to analyze S1T transcript expression in human tissues.
  • Western blot to detect S1T protein expression and homodimerization.
  • Confocal scanning microscopy to determine S1T protein localization.
  • ER-targeted aequorin (erAEQ) to measure ER calcium levels.
  • Overexpression studies in liver-derived cells to assess apoptosis induction.

Main Results:

  • Two SERCA1 splice variants (S1Ts) were identified, encoding truncated proteins unable to bind calcium.
  • S1T transcripts are differentially expressed in various adult and fetal human tissues, excluding skeletal muscle and heart.
  • S1T proteins colocalize with SERCA2b in the ER membrane and reduce ER calcium levels.
  • S1T proteins increase ER calcium leakage, suggesting cation channel activity, and induce apoptosis when overexpressed in liver cells.

Conclusions:

  • S1T proteins represent a novel mechanism for modulating ER calcium accumulation in nonmuscle cells.
  • S1T proteins may function as cation channels and play a significant role in the control of apoptosis.

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