Coronin 1A Expression in Human Astroglia, its Function in Physiology and Astrogliosis in HIV-1 Neuropathogenesis

Abstract

In most neurodegenerative disorders, including neuroAIDS, reactive astroglia are detrimental to the neuronal population. Calcium and its downstream regulators play a central role in mediating glial activation. Coronin 1A, an acting binding protein, majorly reported in cells of hematopoietic origin, regulates cell activity in a calcium-dependent manner, but its role in astroglial physiology and astrogliosis is largely unknown. Using a well-characterized primary culture of human astroglia and neurons, we explored the roles of Coronin 1A in astroglia physiology and the mechanisms by which it facilitates reactive astrogliosis. In this study, we report for the first time, that human primary astroglia express Coronin 1A, and it plays activity-dependent roles in events such as PLCγ1 phosphorylation followed by Calcium mobilization from the intracellular stores. HIV-1 Tat, a potent neurotoxicant that induces astrogliosis, enhances the expression of Coronin 1A, apart from affecting GFAP and pro-inflammatory molecules. Downregulation of Coronin 1A ameliorated the HIV-1 Tat-induced deleterious effects of reactive astroglia, measured as enhanced GFAP expression and release of IL-6, and Glutamate and thus reduced glia-mediated neurodegeneration. Our findings also suggest that out of a pool of dysregulated miRNAs studied by us, hsa-miR-92b-5p regulates Coronin 1A expression which further facilitates reactive astrogliosis under the effect of HIV-1 Tat. These findings highlight the novel roles of Coronin 1A in regulating the astroglial physiology and astrogliosis observed in HIV-1 neuropathogenesis.