Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells |
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Authors: | E. Malissein M. Verdier M. H. Ratinaud D. Troutaud |
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Affiliation: | (1) EA 3842, “Homéostasie Cellulaire & Pathologies,” Limoges, France;(2) EA 3842, “Homéostasie Cellulaire & Pathologies,” Faculté de Médecine, 2 rue du Dr Marcland, 87025 Limoges Cédex, France |
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Abstract: | The activity of Bad, a pro-apoptotic protein, is regulated by reversible phosphorylation. Moreover, sequestration of Bad within subcellular compartments may be a new mechanism of apoptosis regulation. In this study, we report that Bad interacts with 14-3-3 protein in WEHI-231 immature B cells. This association is disrupted following BCR stimulation in correlation with Bad translocation to mitochondria and apoptosis. Confocal microscopy was further used to examine the co-localization of Bad with lipid rafts in WEHI-231 and murineex vivoB cells. Bad was found colocalized to lipid rafts in freshly isolated mature B lymphocytes, in contrast to immature cells. Finally, co-immunoprecipitation experiments performed on WEHI-231 B cells revealed that PP1α interacts with Bcl-2 and Bad, and dissociation of the complex was found correlated with appearance of apoptosis. Bcl-2 seemed to be required to assemble the complex which may regulate Bad phosphorylation status and consequently cell survival. Collectively, present data outline the role of Bad trafficking in the BCR-mediated apoptosis and suggest that differences in intracellular Bad trafficking may be involved in the differential outcome of BCR signaling. |
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Keywords: | apoptosis Bad BCR mitochondria phospho-Bad rafts |
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