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Updated: Jan 15, 2026

Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
Excitatory amino acid transporters support mast cell degranulation via α-KG-mediated methylation of Spp1
Zhending Gan1,2, Yaoyao Xia3, Peng Bin1
1State Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory of Lingnan Modern Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, China.
Abstract:
Excitatory amino acid transporters (EAATs) mediate the progression of inflammatory diseases. However, the involvement of EAATs in the activation of mast cells (MCs) and MC-associated diseases remains unclear. Here, we demonstrate that EAAT2 expression (encoded by Slc1a2) directed by immunoglobulin E (IgE)-mediated high-affinity IgE receptor (FcεRI)-p38 signaling is indispensable for MC degranulation through osteopontin (OPN, encoded by Spp1). Mechanistically, EAAT2 regulates intracellular glutamate/alpha-ketoglutarate/reactive oxygen species (ROS) metabolism to reduce the DNA and histone H3K9 methylation of Spp1. Most importantly, MC-specific depletion of Slc1a2 alleviates the allergic response in mice, and EAAT2 expression is positively correlated with MC-associated diseases in humans. Taken together, our findings establish a mechanistic link between amino acid transporters and epigenetic modifications with MC activation and provide potential therapeutic targets for allergic diseases.
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