ArticleCellular signalling2021
RGS10 physically and functionally interacts with STIM2 and requires store-operated calcium entry to regulate pro-inflammatory gene expression in microglia.
Article in Cellular signalling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- FOXM1 downregulation contributes to sevoflurane-induced microglial dysfunction via transcriptional downregulation of RGS10.Experimental brain research · 2026Article
- Regulator of G protein signaling 10: a critical regulator of chronic systemic inflammation in parkinson's disease.Journal of neuroinflammation · 2026Review
- RGS10 differentially modulates NFKB subunit transcription and inflammatory cytokine profiles in peritoneal macrophages.bioRxiv : the preprint server for biology · 2026Article
- The limited role of RGS10 on NFκB and cytokine transcript levels in peritoneal macrophages under the influence of opioid analgesics.PloS one · 2026Article
- Combined treatment targeting Ca2+ store mediated Ca2+ release and store-operated calcium entry reduces secondary axonal degeneration and improves functional outcome after SCI.Experimental neurology · 2025Article
- RGS10 attenuates systemic immune dysregulation induced by chronic inflammatory stress.Journal of neuroinflammation · 2025Article
- New insights into the stromal interaction molecule 2 function and its impact on the immunomodulation of tumor microenvironment.Cell & bioscience · 2024Review
- RGS10 mitigates high glucose-induced microglial inflammation via the reactive oxidative stress pathway and enhances synuclein clearance in microglia.Frontiers in cellular neuroscience · 2024Article
- STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.Cellular and molecular life sciences : CMLS · 2023Article
- Targeting Store-Operated Calcium Entry Regulates the Inflammation-Induced Proliferation and Migration of Breast Cancer Cells.Biomedicines · 2023Article
- Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- TRPV1 stimulation increased oxidative neurotoxicity and apoptosis in the glia cell membrane but not in the perinuclear area: An evidence of TRPV1 subtype.Metabolic brain disease · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic activation of microglia is a driving factor in the progression of neuroinflammatory diseases, and mechanisms that regulate microglial inflammatory signaling are potential targets for novel therapeutics. Regulator of G protein Signaling 10 is the most abundant RGS protein in microglia, where it suppresses inflammatory gene expression and reduces microglia-mediated neurotoxicity. In particular, microglial RGS10 downregulates the expression of pro-inflammatory mediators including cyclooxygenase 2 (COX-2) following stimulation with lipopolysaccharide (LPS). However, the mechanism by which RGS10 affects inflammatory signaling is unknown and is independent of its canonical G protein targeted mechanism. Here, we sought to identify non-canonical RGS10 interacting partners that mediate its anti-inflammatory mechanism. Through RGS10 co-immunoprecipitation coupled with mass spectrometry, we identified STIM2, an endoplasmic reticulum (ER) localized calcium sensor and a component of the store-operated calcium entry (SOCE) machinery, as a novel RGS10 interacting protein in microglia. Direct immunoprecipitation experiments confirmed RGS10-STIM2 interaction in multiple microglia and macrophage cell lines, as well as in primary cells, with no interaction observed with the homologue STIM1. We further determined that STIM2, Orai channels, and the calcium-dependent phosphatase calcineurin are essential for LPS-induced COX-2 production in microglia, and this pathway is required for the inhibitory effect of RGS10 on COX-2. Additionally, our data demonstrated that RGS10 suppresses SOCE triggered by ER calcium depletion and that ER calcium depletion, which induces SOCE, amplifies pro-inflammatory genes. In addition to COX-2, we also show that RGS10 suppresses the expression of pro-inflammatory cytokines in microglia in response to thrombin and LPS stimulation, and all of these effects require SOCE. Collectively, the physical and functional links between RGS10 and STIM2 suggest a complex regulatory network connecting RGS10, SOCE, and pro-inflammatory gene expression in microglia, with broad implications in the pathogenesis and treatment of chronic neuroinflammation.
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