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

作者: Mounia Chami , Devrim Gozuacik , David Lagorce , Marisa Brini , Pierre Falson

DOI: 10.1083/JCB.153.6.1301

关键词: CalciumSERCAMolecular biologyBiologyCalcium signalingCytosolCalcium-Transporting ATPasesCell biologyEndoplasmic reticulumWestern blotCalcium ATPase

摘要: By pumping calcium from the cytosol to ER, sarco/endoplasmic reticulum ATPases (SERCAs) play a major role in control of signaling. We describe two SERCA1 splice variants (S1Ts) characterized by exon 4 and/or 11 splicing, encoding COOH terminally truncated proteins, having only one seven calcium-binding residues, and thus unable pump calcium. As shown semiquantitative RT-PCR, S1T transcripts are differentially expressed several adult fetal human tissues, but not skeletal muscle heart. proteins expression was detected Western blot nontransfected cell lines. In transiently transfected cells, homodimers were revealed using mildly denaturing conditions. shown, confocal scanning microscopy, colocalize with endogenous SERCA2b into ER membrane. Using ER-targeted aequorin (erAEQ), we have found that reduce reverse elevation loading induced SERCA2b. Our results also show increase leakage consistent hypothesis cation channel formed homodimers. Finally, when overexpressed liver-derived significantly induce apoptosis. These data reveal further mechanism modulating Ca2+ accumulation nonmuscle cells highlight relevance

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