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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.

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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.

Item Type: Journal Item
Copyright Holders: 2004 The Rockefeller University Press
ISSN: 0021-9525
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetCA85804National Institutes of Health
Not SetNot SetInternational Union Against Cancer Yamagiwa-Yoshida Memorial International Cancer Study grant
Not SetNot SetFondecyt 1020927 and 7020927
Not SetNot SetBBSRC (Biotechnology and Biological Sciences Research Council)
Not SetNot SetHuman Frontier Science Programme
Not SetCA42755National Institutes of Health
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 34882
Depositing User: Martin Bootman
Date Deposited: 13 Mar 2013 14:06
Last Modified: 08 Dec 2018 17:43
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