| First Author | Lisak D | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 2 | Pages | 358-68 |
| PubMed ID | 26470731 | Mgi Jnum | J:258642 |
| Mgi Id | MGI:6142420 | Doi | 10.1038/cdd.2015.115 |
| Citation | Lisak D, et al. (2016) BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival. Cell Death Differ 23(2):358-68 |
| abstractText | The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-kappaB (nuclear factor-kappa light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca(2+) levels, suggesting an exhausted mitochondrial Ca(2+) buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca(2+) homeostasis in lymphocytes. |
