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

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 Gα q 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 Gα q 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 Gα q releases these proteins to enable the formation of stress granules. Together, our data suggest a link between Gα q -coupled signals and protein translation through stress granule formation.