The G protein regulator AGS-3 allows C. elegans to alter behaviors in response to food deprivation

Abstract

Behavioral responses to food deprivation are a fundamental aspect of nervous system function in all animals. In humans, these behavioral responses prevent dieting from being an effective remedy for obesity. Several signaling molecules in the mammalian brain act through G proteins of the Gαi/o family to mediate responses to food restriction. The mechanisms for neural response to food deprivation may be conserved across species, allowing the power of genetic model organisms to generate insights relevant to the problem of human obesity. In a recent study, we found that C. elegans uses Gαo signaling to mediate a number of behavioral changes that occur after food deprivation. Food deprivation causes biochemical changes in the G Protein Regulator (GPR) domain protein AGS-3 and AGS-3, together with the guanine nucleotide exchange factor RIC-8, activates Gαo signaling to alter food-seeking behavior. These proteins are all conserved in the human brain. Thus the study of behavioral responses to food deprivation in C. elegans may reveal the details of conserved molecular mechanisms underlying neural responses to food deprivation.

Tubulin, actin and heterotrimeric G proteins: Coordination of signaling and structure

“…Animals deficient in Gαo or AGS3 fail to modify certain behaviors in response to short-term food deprivation, such as egg-laying rates and food-seeking [92]. Furthermore, AGS3 moves from a Triton X-100 insoluble to a soluble fraction in whole animal lysate within several hours of food deprivation[93]. This likely reflects intracellular information transfer involving cytoskeletal components that is mediated by G proteins and their associates.…”

Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans

“…These results lead to a model in which food deprivation leads to a physical change in AGS-3, allowing it to activate Gα o signaling to induce behavioral changes appropriate for the food-deprived state of the animal. It will be fascinating to see if this role of AGS-3 in mediating response to food deprivation is conserved in mammals (Hofler and Koelle, 2012: PMID 24058824).…”