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.

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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
• 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