Cross-Genome Clustering of Human and C. elegans G-Protein Coupled Receptors

Joo

et al. 2019

IJMS

Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal β-oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid β-oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of pheromics (pheromone omics) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones.

Section: Discussionmentioning

confidence: 99%

Ascaroside Pheromones: Chemical Biology and Pleiotropic Neuronal Functions

Joo

et al. 2019

IJMS

“…G proteins mediate stimulus perception by G-protein-coupled receptors (GPCR), in addition to other regulatory proteins. In humans, there are about 1000 GPCR, representing the largest group of cell surface receptors encoded by mammalian genome ( Nagarathnam et al, 2012 ). It is estimated that about 60% of all drugs currently available target G-protein-based pathways and G protein component disorders have been found to cause various genetic diseases ( Assmann, 2004 ).…”

Section: Reactive Oxygen Species At the Cross-roadmentioning

confidence: 99%

Global Plant Stress Signaling: Reactive Oxygen Species at the Cross-Road

2016

Current technologies have changed biology into a data-intensive field and significantly increased our understanding of signal transduction pathways in plants. However, global defense signaling networks in plants have not been established yet. Considering the apparent intricate nature of signaling mechanisms in plants (due to their sessile nature), studying the points at which different signaling pathways converge, rather than the branches, represents a good start to unravel global plant signaling networks. In this regard, growing evidence shows that the generation of reactive oxygen species (ROS) is one of the most common plant responses to different stresses, representing a point at which various signaling pathways come together. In this review, the complex nature of plant stress signaling networks will be discussed. An emphasis on different signaling players with a specific attention to ROS as the primary source of the signaling battery in plants will be presented. The interactions between ROS and other signaling components, e.g., calcium, redox homeostasis, membranes, G-proteins, MAPKs, plant hormones, and transcription factors will be assessed. A better understanding of the vital roles ROS are playing in plant signaling would help innovate new strategies to improve plant productivity under the circumstances of the increasing severity of environmental conditions and the high demand of food and energy worldwide.

“…Their genomes have been completely sequenced and are fully annotated and a vast range of functional resources exists and numerous GPCRs have been characterized (Consortium, 1998; Adams et al, 2000; Keating et al, 2003). In the roundworm, GPCRs account for approximately 5% of the genome (there are more than 1000) and the chemoreceptor genes, which are involved in chemoreception of environmental stimuli are unique in nematodes and are also the most abundant and diverse (Schioth and Fredriksson, 2005; Robertson and Thomas, 2006; Nagarathnam et al, 2012). In the fruit fly, approximately 200 GPCRs (1% of the genome) are predicted and the gustatory/taste receptors (Montell, 2009) are specific to insects although a quarter share sequence homology with vertebrate neurohormone receptors (Keating et al, 2003; Fredriksson and Schioth, 2005; Hauser et al, 2006; Nagarathnam et al, 2012).…”

Section: The Invertebrate Gpcrs Superfamilymentioning

confidence: 99%

“…In the roundworm, GPCRs account for approximately 5% of the genome (there are more than 1000) and the chemoreceptor genes, which are involved in chemoreception of environmental stimuli are unique in nematodes and are also the most abundant and diverse (Schioth and Fredriksson, 2005; Robertson and Thomas, 2006; Nagarathnam et al, 2012). In the fruit fly, approximately 200 GPCRs (1% of the genome) are predicted and the gustatory/taste receptors (Montell, 2009) are specific to insects although a quarter share sequence homology with vertebrate neurohormone receptors (Keating et al, 2003; Fredriksson and Schioth, 2005; Hauser et al, 2006; Nagarathnam et al, 2012). Recently GPCRs were also characterized in the genome of two Platyhelminthes, the blood fluke Schistosoma mansoni and the planarian Schmidtea mediterranea and a similar gene repertoire to vertebrates has been characterized.…”

Section: The Invertebrate Gpcrs Superfamilymentioning

confidence: 99%

Feeding and the Rhodopsin Family G-Protein Coupled Receptors in Nematodes and Arthropods

et al. 2012

In vertebrates, receptors of the rhodopsin G-protein coupled superfamily (GPCRs) play an important role in the regulation of feeding and energy homeostasis and are activated by peptide hormones produced in the brain-gut axis. These peptides regulate appetite and energy expenditure by promoting or inhibiting food intake. Sequence and function homologs of human GPCRs involved in feeding exist in the nematode roundworm, Caenorhabditis elegans (C. elegans), and the arthropod fruit fly, Drosophila melanogaster (D. melanogaster), suggesting that the mechanisms that regulate food intake emerged early and have been conserved during metazoan radiation. Nematodes and arthropods are the most diverse and successful animal phyla on Earth. They can survive in a vast diversity of environments and have acquired distinct life styles and feeding strategies. The aim of the present review is to investigate if this diversity has affected the evolution of invertebrate GPCRs. Homologs of the C. elegans and D. melanogaster rhodopsin receptors were characterized in the genome of other nematodes and arthropods and receptor evolution compared. With the exception of bombesin receptors (BBR) that are absent from nematodes, a similar gene complement was found. In arthropods, rhodopsin GPCR evolution is characterized by species-specific gene duplications and deletions and in nematodes by gene expansions in species with a free-living stage and gene deletions in representatives of obligate parasitic taxa. Based upon variation in GPCR gene number and potentially divergent functions within phyla we hypothesize that life style and feeding diversity practiced by nematodes and arthropods was one factor that contributed to rhodopsin GPCR gene evolution. Understanding how the regulation of food intake has evolved in invertebrates will contribute to the development of novel drugs to control nematodes and arthropods and the pests and diseases that use them as vectors.