Stimulation of phospholipase Cβ1 by Gαq promotes the assembly of stress granule proteins

Abstract

Description Stimulation of Gαq-coupled GPCRs releases PLCβ1 from stress granule–associated proteins, enabling their aggregation. Stressing out with PLCβ1 When cells are subjected to various environmental stresses, they generate stalled translational complexes known as stress granules to inhibit global protein synthesis and enable the production of proteins that can alleviate the stress. The phospholipase PLCβ1 is activated at the plasma membrane by Gαq-coupled GPCRs to generate second messengers. Qifti et al. found that a fraction of PLCβ1 in the cytosol interacted with stress granule–associated proteins in various cell types under basal conditions. Activation of Gαq-coupled GPCRs recruited PLCβ1 to the plasma membrane, releasing the stress granule–associated proteins and enabling their aggregation. These data add a new role for PLCβ1 and suggest a link between GPCR signals and protein translation. During adverse conditions, mammalian cells suppress protein production by sequestering the translational machinery in membrane-less organelles known as stress granules. Here, we found that activation of the G protein subunit Gαq promoted the formation of particles that contained stress granule proteins through a mechanism linked to a cytosolic fraction of phospholipase Cβ1 (PLCβ1). In experiments with PC12 and A10 cells, we showed that under basal conditions, cytosolic PLCβ1 bound to stress granule–associated proteins, including PABPC1, eIF5A, and Ago2. Knockdown of cytosolic PLCβ1 with siRNA or promoting its relocalization to the plasma membrane by activating Gαq resulted in the formation of particles containing these stress granule–associated proteins. Our studies showed that the composition of these particles resembled those formed under osmotic stress and were distinct from those formed in response to other types of stress. Our results fit a simple thermodynamic model in which cytosolic PLCβ1 solubilizes stress granule proteins such that its movement to activated Gαq releases these proteins to enable the formation of stress granules. Together, our data suggest a link between Gαq-coupled signals and protein translation through stress granule formation.