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Bax Inhibitor-1 is a novel IP3 receptor-interacting and -sensitizing protein

Cell Death and Disease
Nature Publishing Group
Publication Date
DOI: 10.1038/cddis.2012.103
  • Correspondence
  • Biology


Bax Inhibitor-1 is a novel IP3 receptor-interacting and -sensitizing protein Correspondence Bax Inhibitor-1 is a novel IP3 receptor-interacting and -sensitizing protein S Kiviluoto1, L Schneider2, T Luyten1, T Vervliet1, L Missiaen1, H De Smedt1, JB Parys1, A Methner2 and G Bultynck*,1 Cell Death and Disease (2012) 3, e367; doi:10.1038/cddis.2012.103; published online 9 August 2012 Subject Category: Internal Medicine Dear Editor, Bax Inhibitor-1 (BI-1) is an evolutionary conserved endo- plasmic reticulum (ER)-located protein that protects against ER stress-induced apoptosis.1 This function has been closely related to its ability to permeate Ca2þ from the ER2 and to lower the steady-state [Ca2þ ]ER. 3 BI-1 may function as an Hþ /Ca2þ -antiporter2 or Ca2þ channel.4 Recently, BI-1 was proposed as a negative regulator of autophagy through IRE1a.5 However, recent findings indicate that BI-1 may promote autophagy.6 The latter required the presence of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R). The observations were explained through BI-1-enhanced IP3R activity, which lowered steady-state [Ca2þ ]ER, reducing ER-mitochondrial Ca2þ transfer and decreasing mito- chondrial bio-energetics.7 However, direct evidence that BI-1 binds to IP3Rs and sensitizes IP3-induced Ca 2þ release (IICR) is lacking. Therefore, we studied the regulation of IP3R function by BI-1 (see Supplementary Information for Methods). We constructed a 5xMyc-BI-1-expression plasmid, allowing the detection and purification of ectopically expressed BI-1 from transfected HeLa cells using anti-Myc- agarose beads (Figure 1a). Using isoform-specific IP3R antibodies, we demonstrated the co-immunoprecipitation of IP3R1 and IP3R3 with 5xMyc-BI-1 from HeLa cell lysates. Next, we screened for the subdomain of BI-1 responsible for IP3R interaction. We found that a synthetic Flag-tagged peptide containing BI-1’s Ca2þ -channel pore domain (CTP1; amino acids 198–217 of human BI-1) interacted with IP3R1 (Figure 1b). Lysate

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