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.
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 el...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1826301725762387968 |
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| author | Chen, R Valencia, I Zhong, F McColl, K Roderick, H Bootman, MD Berridge, M Conway, S Holmes, AB Mignery, G Velez, P Distelhorst, C |
| author_facet | Chen, R Valencia, I Zhong, F McColl, K Roderick, H Bootman, MD Berridge, M Conway, S Holmes, AB Mignery, G Velez, P Distelhorst, C |
| author_sort | Chen, R |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T05:36:43Z |
| format | Journal article |
| id | oxford-uuid:e4249806-ed70-4f82-8660-ed2f318997f3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:36:43Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:e4249806-ed70-4f82-8660-ed2f318997f32022-03-27T10:14:34ZBcl-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.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e4249806-ed70-4f82-8660-ed2f318997f3EnglishSymplectic Elements at Oxford2004Chen, RValencia, IZhong, FMcColl, KRoderick, HBootman, MDBerridge, MConway, SHolmes, ABMignery, GVelez, PDistelhorst, CInositol 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. |
| spellingShingle | Chen, R Valencia, I Zhong, F McColl, K Roderick, H Bootman, MD Berridge, M Conway, S Holmes, AB Mignery, G Velez, P Distelhorst, C 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. |
| 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
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