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

Regulator of G protein signaling 10 (RGS10) is a GTPase activating protein, selective for Gαi, that has been proposed to play a role in suppressing microglial-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-2WT) and absent (RGS10-/-) RGS10 expression under basal and IFNγ-treated conditions. RGS10 loss altered expression of 1,579 genes in unstimulated cells and 2,142 genes under IFNγ-stimulated conditions. In addition to changes in GPCR signaling, altered processes in RGS10-/- cells, under basal and stimulated conditions, included cell migration, adhesion, cytokine production and cell development. Key cell adhesion genes such as Mmp9 and Thbs1 were downregulated in RGS10-/- cells regardless of stimuli. Other genes such as Icam1 and Il1b displayed significantly lower expression only in IFNγ-stimulated RGS10-/- cells compared to their WT counterpart. Loss of RGS10 increased BV-2 cell migration, and IFNγ stimulation led to a reduction in migration of both BV-2WT and RGS10-/- cells. The effect of RGS10 on migration could only partially be blocked by the Gαi 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.