| Title: |
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. |
| Authors: |
Chen, R; Valencia, I; Zhong, F; McColl, K; Roderick, H; Bootman, MD; Berridge, M; Conway, S; Holmes, AB; Mignery, G; Velez, P; Distelhorst, C |
| Publication Year: |
2016 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1083/jcb.200309146 |
| DOI: |
10.1083/jcb.200309146 |
| Availability: |
https://doi.org/10.1083/jcb.200309146; https://ora.ox.ac.uk/objects/uuid:e4249806-ed70-4f82-8660-ed2f318997f3 |
| Rights: |
info:eu-repo/semantics/embargoedAccess |
| Accession Number: |
edsbas.2E873074 |
| Database: |
BASE |