Bioinformatic analysis identifies RGS10 as a modulator of BV-2 microglia migration

Regulator of G protein signaling 10 (RGS10) is a GTPase activating protein, selective for Gα_i, that has been proposed to play a role in suppressing microglia-driven neuroinflammation. RGS10 expression in microglia is suppressed by inflammatory stimuli and aging, and loss of RGS10 is associated with increased cytokine expression and neurodegeneration. Conversely, RGS10 overexpression provides protection against inflammatory stimuli in rodent models, however the mechanisms by which RGS10 exerts this protective effect are unknown. To understand the neuroprotective functions of RGS10 in microglia, we completed RNA-Seq analysis in the murine microglial cell line BV-2 with intact (BV-2^WT) and absent (RGS10^-/-) RGS10 expression, with or without interferon-γ (IFNγ)-stimulation. We identified genes whose expression were altered as a result of RGS10 loss, IFNγ stimulation, or both. As expected, RGS10 loss resulted in changes in processes such as GPCR signaling and synaptic signaling. However, this analysis also revealed that processes such as cell migration and adhesion were altered in RGS10^-/- cells, under both basal and IFNγ-stimulated conditions. Key cell adhesion genes such as Mmp9 and Thbs1 were downregulated in RGS10^-/- cells regardless of stimuli. Experimentally, loss of RGS10 increased BV-2 cell migration, and IFNγ stimulation led to a reduction in migration of both BV-2^WT and RGS10^-/- cells. The effect of RGS10 on migration could only partially be blocked by the Gα_i inhibitor Pertussis toxin (PTX), suggesting involvement of both G protein-dependent and -independent mechanisms. Altogether, these results suggest a novel role for RGS10 in reducing microglial migration through regulation of cell adhesion genes.