Functional expression of the seven-transmembrane HIV-1 co-receptor APJ in neural cells

APT is a recently described seven-transmembrane (7TM) receptor that is abun dantly expressed in the central nervous system (CNS). This suggests an impo rtant role for APT in neural development and/or function, but neither its c ellular distribution nor its function have been defined, APT can also serve as a co-receptor with CD4 for fusion and infection by some strains of huma n immunodeficiency virus (HIV-1) in vitro, suggesting a role in HIV neuropa thogenesis if it were expressed on CD4-positive CNS cells. To address this, we examined APT expression in cultured neurons, astrocytes, oligodendrocyt es, microglia and monocyte-derived macrophages utilizing both immunocytoche mical staining with a polyclonal anti-APT antibody and RT-PCR. We also anal yzed the ability of a recently identified APT peptide ligand, apelin, to in duce calcium elevations in cultured neural cells, APT was expressed at a hi gh level in neurons and oligodendrocytes, and at lower levels in astrocytes . In contrast, APT was not expressed in either primary microglia or monocyt e-derived macrophages. Several forms of the APT peptide ligand induced calc ium elevations in neurons. Thus, APT is selectively expressed in certain CN S cell types and mediates intracellular signals in neurons, suggesting that APT may normally play a role in signaling in the CNS, However, the absence of APT expression in microglia and macrophages, the prinicpal CD4-positive cell types in the brain, indicates that APT is unlikely to mediate HIV-1 i nfection in the CNS.