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- 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, 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; Distelhorst, Clark W.
- Abstract
Inositol 1,4,5-trisphosphate (lnsP3) receptors (lnsP3Rs) 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 lnsP3-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 lnsP3Rs because responses to both anti-CD3 antibody and a cell-permeant lnsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of lnsP3, without decreasing luminal calcium concentration. Further- more, BcI-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. BcI-2 and lnsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with lnsP3Rs inhibits lnsP3R activation and thereby regulates lnsP3-induced calcium release from the ER.
- Subjects
INOSITOL phosphates; ENDOPLASMIC reticulum; IMMUNOGLOBULINS; MACROMOLECULES; GEL electrophoresis; CYTOSOL
- Publication
Journal of Cell Biology, 2004, Vol 166, Issue 2, p193
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200309146