Biphasic regulation of InsP3 receptor gating by dual Ca2+ release channel BH3-like domains mediates Bcl-xL control of cell viability
Abstract
Changes in Ca2+ concentration in the cell play important roles in cell life and death decisions. Antiapoptotic Bcl-2 family proteins help protect cells from dying by interacting with proteins at mitochondria and endoplasmic reticulum. At the endoplasmic reticulum, antiapoptotic Bcl-2 proteins interact with InsP3R Ca2+ channels that release Ca2+ into the cytoplasm. However, it is controversial how they interact with the InsP3R, as well as the functional consequences of the interactions. We found that antiapoptotic Bcl-xL interacts with InsP3Rs by unique mechanisms that change the activity of the channel depending on its concentration. We also found that disrupting these interactions diminishes cell viability. Our results provide a unifying model of the effects of antiapoptotic Bcl-2 proteins on the InsP3R.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2016
- DOI:
- 10.1073/pnas.1517935113
- Bibcode:
- 2016PNAS..113E1953Y