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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).
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.
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About
- Item ORO ID
- 34882
- Item Type
- Journal Item
- ISSN
- 0021-9525
- Project Funding Details
-
Funded Project Name Project ID Funding Body Not Set CA85804 National Institutes of Health Not Set Not Set International Union Against Cancer Yamagiwa-Yoshida Memorial International Cancer Study grant Not Set Not Set Fondecyt 1020927 and 7020927 Not Set Not Set BBSRC (Biotechnology and Biological Sciences Research Council) Not Set Not Set Human Frontier Science Programme Not Set CA42755 National Institutes of Health - Academic Unit or School
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Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM) - Copyright Holders
- © 2004 The Rockefeller University Press
- Depositing User
- Martin Bootman