Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate

Chen, Rui; Valencia, Ignacio; Zhong, Fei; McColl, Karen S.; Roderick, H. Llewelyn; Bootman, Martin D.; Berridge, Michael J.; Conway, Stuart J.; Holmes, Andrew B.; Mignery, Gregory A.; Velez, Patricio and Distelhorst, Clark W. (2004). Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. The Journal of Cell Biology, 166(2) pp. 193–203.

DOI: https://doi.org/10.1083/jcb.200309146

Abstract

Inositol 1,4,5-trisphosphate (InsP₃) receptors (InsP₃Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP₃-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP₃Rs because responses to both anti-CD3 antibody and a cell-permeant InsP₃ ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP₃, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP₃Rs reconstituted into lipid bilayers. Bcl-2 and InsP₃Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP₃Rs inhibits InsP3R activation and thereby regulates InsP₃-induced calcium release from the ER.

Viewing alternatives

Metrics

Item Actions

Export

You can export this page using these formats Digital Object Identifier - DOI