Bcl-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region |
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Authors: | Chami Mounia Prandini Andrea Campanella Michelangelo Pinton Paolo Szabadkai Gyorgy Reed John C Rizzuto Rosario |
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Affiliation: | Department of Experimental and Diagnostic Medicine, Section of General Pathology and the Interdisciplinary Center for the Study of Inflammation, University of Ferrara, 44100 Ferrara, Italy. |
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Abstract: | Recent work has shown that Bcl-2 and other anti-apoptotic proteins partially deplete the endoplasmic reticulum (ER) Ca(2+) store and that this alteration of Ca(2+) signaling reduces cellular sensitivity to apoptotic stimuli. We expressed in HeLa cells Bcl-2, Bax, and Bcl-2/Bax chimeras in which the putative pore-forming domains of the two proteins (alpha 5-alpha 6) were mutually swapped, comparing the effects on Ca(2+) signaling of the two proteins and relating them to defined molecular domains. The results showed that only Bcl-2 reduces ER Ca(2+) levels and that this effect does not depend on the alpha 5-alpha 6 helices of this oncoprotein. Soon after its expression, Bax increased ER Ca(2+) loading, with ensuing potentiation of mitochondrial Ca(2+) responses. Then the cells progressed into an apoptotic phenotype (which included drastic reductions of cytosolic and mitochondrial Ca(2+) responses and alterations of organelle morphology). These results provide a coherent scenario that high-lights a primary role of Ca(2+) signals in deciphering apoptotic stimuli. |
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