| 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, KS; Roderick, HL; Bootman, MD; Berridge, MJ; Conway, SJ; Holmes, AB; Mignery, GA; Velez, P; Distelhorst, CW |
| Publisher Information: |
Rockefeller University Press |
| Publication Year: |
2004 |
| Collection: |
The University of Melbourne: Digital Repository |
| 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 |
| ISSN: |
0021-9525 |
| Relation: |
pii: jcb.200309146; https://hdl.handle.net/11343/303833 |
| Availability: |
https://hdl.handle.net/11343/303833 |
| Rights: |
https://creativecommons.org/licenses/by-nc-sa/4.0 ; CC BY-NC-SA |
| Accession Number: |
edsbas.BBE28C3 |
| Database: |
BASE |