title: AGS-3 alters Caenorhabditis elegans behavior after food deprivation via RIC-8 activation of the neural G protein G αo.
abstract: Proteins containing the G protein regulator (GPR) domain bind the major neural G protein Gα(o) in vitro. However, the biological functions of GPR proteins in neurons remain undefined, and based on the in vitro activities of GPR proteins it is unclear whether these proteins activate or inhibit G protein signaling in vivo. We found that the conserved GPR domain protein AGS-3 activates Gα(o) signaling in vivo to allow Caenorhabditis elegans to alter several behaviors after food deprivation, apparently so that the animals can more effectively seek food. AGS-3 undergoes a progressive change in its biochemical fractionation upon food deprivation, suggesting that effects of food deprivation are mediated by modifying this protein. We analyzed one C. elegans food-regulated behavior in depth; AGS-3 activates Gα(o) in the ASH chemosensory neurons to allow food-deprived animals to delay response to the aversive stimulus octanol. Genetic epistasis experiments show the following: (1) AGS-3 and the guanine nucleotide exchange factor RIC-8 act in ASH in a mutually dependent fashion to activate Gα(o); (2) this activation requires interaction of the GPR domains of AGS-3 with Gα(o); and (3) Gα(o)-GTP is ultimately the signaling molecule that acts in ASH to delay octanol response. These results identify a biological role for AGS-3 in response to food deprivation and indicate the mechanism for its activation of Gα(o) signaling in vivo.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8024, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hofler
authors.forename: Michael R
authors.initials: MR
authors.lastname: Koelle
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004330:Drosophila; D005508:Food Deprivation / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism* / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C413418:RIC-8 protein, C elegans; D019206:GTP-Binding Protein alpha Subunits, Gi-Go