Subcellular compartmentalization of CD38 in non- hematopoietic cells: A study to characterize its functional role in mitochondria

Abstract

CD38 is a type II transmembrane glycoprotein known for its involvement in the metabolism of cADPR. To study the functional role of CD38 in different organelles, CD38 with organelle specific targeting signal was transiently expressed in COS-7cell. The specific localization of the targeted CD38 was examined by immunocytochemistry studies. CD38 expressed in mitochondria was functionally active and localized on the outer mitochondrial membrane (OMM). This observation was further supported by experimental results acquired using mouse brain tissue. Immunolabelling studies using electron microscopy together with digitonin/proteinase K assay determined the localization of CD38 to the OMM with its catalytic site facing the cytosol. cADPR produced by mitochondrial CD38 elicited rapid calcium release from the endoplasmic reticulum. This response is sensitive to treatment by 8-Bromo-cADPR, a cADPR antagonist. This study therefore demonstrated the expression of functionally active CD38 in mitochondria, which may participate in a novel pathway for intracellular Ca2+ signalling in non-hematopoietic cells.