Repeated Activation of Gαq by neurotransmitters causes age-dependent accumulation of stress granules inC.elegans

Abstract

ABSTRACTGαq proteins mediate signals from neurotransmitters to transduce calcium signals. In PC12 cells, we have shown that Gαq stimulation results in retraction of neurites and induces the formation of stress granules that sequester two specific mRNAs,ChbgbandATP5f1b. Here, we show that repeated activation of Gαq inC. elegansadversely reduces lifespan potentially through accumulation of stress granules and inefficient recovery from neurite retraction. In the absence of stimulation, we could not detect significant changes in number of stress granules from Day 1-15 worms. Single Gαq activation increases stress granule size through the enlargement of pre-formed particles with younger worms (Day 1-4) being more responsive than older (Day 8). Repeated Gαq stimulation impacts the number of particles through the assembly of nascent particles. Additionally, we a systematic rise in the number of AGL-1 stress granules with repeated Gαq stimulation suggesting that stress granules accumulate in neurons and sequester mRNAs. This idea is supported by immunofluorescence studies of ATP5f1b as well as changes in peristaltic speed. In addition to stress granule accumulation, we find that repeated Gαq activation results in age-dependent morphological defects in mechanosensory neurons. Taken together, studies show that repeated Gαq activation negatively influences the health ofC.elegans.