Disease relevance of G-protein

• Using a systemic and continuous delivery method based on feeding on a particular strain of transformed Escherichia coli to induce double stranded RNA-mediated interference, we targeted the product of the npr-1 gene, a putative Caenorhabditis elegans homologue of a neuropeptide Y receptor, a G-protein coupled receptor [1].
• Mimicry of a G protein mutation by pertussis toxin expression in transgenic Caenorhabditis elegans [2].

Psychiatry related information on G-protein

• The C. elegans G-protein-coupled receptor SRA-13 inhibits RAS/MAPK signalling during olfaction and vulval development [3].
• A loss-of-function mutation in the npr-1 gene, which encodes a predicted G protein-coupled receptor similar to neuropeptide Y receptors, causes a solitary strain to take on social behavior [4].

High impact information on G-protein

• In C. elegans, gpb-1 encodes the sole Gbeta subunit; therefore, its inactivation should affect all heterotrimeric G protein signaling [5].
• Different G-protein signaling pathways have characteristic effects on behavior, neuronal degeneration, and embryonic development [6].
• On the basis of epistasis analysis, flp-1 gene products appear to signal upstream of a G protein-coupled second messenger system [7].
• Asymmetric division of Drosophila neuroblasts (NBs) and the Caenorhabditis elegans zygote uses polarity cues provided by the Par proteins, as well as heterotrimeric G-protein-signalling that is activated by a receptor-independent mechanism mediated by GoLoco/GPR motif proteins [8].
• G protein-coupled receptor kinases (GRKs) are important regulators of G protein signal transduction that specifically phosphorylate activated GPCRs to terminate signaling [9].

Biological context of G-protein

• The predicted 340 amino acid sequence matches the highly conserved amino acid sequences of previously isolated G-protein beta-subunits from mammals and Drosophila [10].
• Noncell- and cell-autonomous G-protein-signaling converges with Ca2+/mitogen-activated protein kinase signaling to regulate str-2 receptor gene expression in Caenorhabditis elegans [11].
• Our results indicate that alternative splicing plays an important role in promoting molecular diversity of G-protein-linked acetylcholine receptors in C. elegans [12].
• The str family of genes encoding seven-transmembrane G-protein-coupled or serpentine receptors related to the ODR-10 diacetyl chemoreceptor is very large, with at least 197 members in the Caenorhabditis elegans genome [13].
• Metabotropic glutamate receptors (mGluRs) are a class of G-protein-coupled receptors that possess a seven transmembrane region involved in the modulation of excitatory synaptic transmission in the nervous system. mGluR orthologs have been identified in Drosophila, Caenorhabditis elegans, and higher organisms [14].

Anatomical context of G-protein

• Finally, the response to NaCl is modulated by G-protein signalling in the ASI and ADF neurons, a second G-protein pathway in ASH and cGMP signalling in neurons exposed to the body fluid [15].
• These channels, as well as the G-protein Galpha(o), function in neuroendocrine cells to promote release of neurotransmitters that block egg laying until eggs filling the uterus deform the neuroendocrine cells [16].
• Electrophysiological analyses using the Xenopus oocyte system showed that all three GAR-2 isoforms couple to the activation of G-protein-gated inwardly rectifying K+ (GIRK1) channel with similar drug specificity [12].
• Modulation of EGF receptor-mediated vulva development by the heterotrimeric G-protein Galphaq and excitable cells in C. elegans [17].
• Muscarinic acetylcholine receptors regulate the activity of neurons and muscle cells through G-protein-coupled cascades [18].

Associations of G-protein with chemical compounds

• Among the three G-protein-linked acetylcholine receptors (GARs) in Caenorhabditis elegans (C. elegans), GAR-3 is structurally and pharmacologically most similar to mammalian muscarinic acetylcholine receptors (mAChRs) [19].
• A gene encoding the alpha-subunit of a guanine nucleotide binding regulatory protein (G-protein) was isolated from a library of genomic Caenorhabditis elegans DNA [20].
• Receptor signaling studies with mammalian AV12 cells expressing the 5HT1Hc-receptor and the promiscuous G-protein, Galpha15, demonstrated dose-dependent intracellular signals with serotonin acting as an agonist [21].
• mGluRs (metabotropic glutamate receptors) are G-protein-coupled receptors that play an important neuromodulatory role in the brain [22].
• Finally, we found that a knock-out for the HSN-expressed receptor G-protein-coupled acetylcholine receptor 2 (GAR-2) shows a partial defect in the inhibition of egg laying and fails to respond to aldicarb [23].

Physical interactions of G-protein

• This natural variation in behaviour is associated with a single residue difference in NPR-1, a predicted G-protein-coupled neuropeptide receptor related to Neuropeptide Y receptors [24].
• To function in olfactory imprinting, this interneuron pair must express a G protein-coupled chemoreceptor family member encoded by the sra-11 gene [25].

Other interactions of G-protein

• The signaling cascade is only partially dependent on the phospholipase C beta (EGL-8) and is negatively regulated by G alpha(o) [GOA-1 (G-protein, O, alpha subunit family member 1)] and calcium/calmodulin-dependent kinase [UNC-43 (uncoordinated family member 43)] [26].
• Here we show that the same Ca2+/MAPK pathway promotes str-2 expression in the AWC and ASI neurons together with multiple cell-autonomous and noncell-autonomous G-protein-signaling pathways [11].
• The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation [27].
• Here, we describe the characterization of the second G-protein beta-subunit gene gpb-2 [28].
• GAR-3 signaling is enhanced in worms overexpressing gar-3 or lacking GPB-2, a G-protein beta-subunit involved in RGS-mediated inhibition of G(o)alpha- and G(q)alpha-linked pathways [18].

Analytical, diagnostic and therapeutic context of G-protein

• G-protein expression in infective larvae was also investigated by RT-PCR analysis: this stage of the organism was found to resemble the adult more than the microfilaria but differed from the adult in that GS was absent and Gi3 was present [29].
• No other G-protein alpha-subunits were found in microfilariae by Western blotting [29].

References