Neurotransmitter Activation Sequesters Specific mRNAs Into Stress Granules

Abstract

Hormones and neurotransmitters can activate the Gαq / phospholipase Cβ1 (PLCβ1) signaling system eliciting cellular calcium responses. Aside from the plasma membrane, PLCβ1 has a cytosolic population that binds stress granule associated proteins preventing their aggregation, and activation of Gαq shifts PLCβ1 to the membrane releasing bound proteins and promoting the formation of stress granules. The cellular impact of stress granules formed upon routine Gαq protein signaling is unknown. Here, we have characterized Ago2 stress granules formed in response to neurotransmitter activation in cultured PC12 cells. We find these stress granules have a distinct protein composition, and unlike stress granules formed upon heat shock, contain only two mRNA transcripts, chromogranin B, which is involved in secretory function, and ATP synthase 5f1b, which is required for ATP synthesis. Our studies show an unexpected pathway where Gαq/PLCβ regulates the translation of specific proteins.