Chemosensation: molecular mechanisms in worms and mammals

doi:10.1016/S0168-9525(99)01695-9

Trends in Genetics

Volume 15, Issue 4, 1 April 1999, Pages 150-153

https://doi.org/10.1016/S0168-9525(99)01695-9 Get rights and content

Abstract

Communication with the environment and other animals through chemical cues is an essential process for the survival of many multicellular organisms. Specialized signal transduction pathways are employed in chemodetection and the transformation of information into the electrical signals that elicit behaviors. In organisms as diverse as mice and nematodes, similar molecules are involved in the odorant signaling pathways. Studying the mechanisms of signal transduction in these two systems using biochemical, molecular and genetic approaches has elucidated pathways for odor perception and the roles of specific proteins and second messenger molecules in the signaling cascades.

Section snippets

Roles of olfaction in diverse organisms

Most vertebrate species use olfaction as a means to communicate with the environment and other animals; the ability to smell is essential for the survival of many organisms. The olfactory system is necessary for suckling and nurturing responses. Humans can recognize at least 10 000 different odors, while most mammals possess considerably greater sensitivity and discriminating abilities. Odor perception also elicits emotional and cognitive responses. In order to distinguish among the large

Molecular approaches to olfactory transduction

Over a decade ago, the report of odorant-stimulated GTP-dependent adenylyl cyclase activity in frog olfactory cilia20, 21 marked the beginning of a search for proteins involved in transforming external chemical cues into the electrical stimuli processed by the brain and developed into odor perception. An understanding of the mechanisms for detection of light stimuli by the visual system, the best-characterized sensory modality, provided the framework for the identification of components of the

Signaling pathways in mammals and worms

The initial biochemical description of the olfactory transduction process in mammals has recently been supplemented by molecular genetic efforts that have largely supported the hypothesis of a cAMP-mediated transduction pathway for all odorants. Mice that lack components of this pathway, generated by homologous recombination, display profound reductions or even an absence of physiological responses to odorants. EOGs were used to measure the integrated electrical activity of the responding

Pheromone detection in mammals

The main olfactory system of mammals is responsible for the recognition of volatile odorant compounds. Distinct systems have evolved in many higher eukaryotes for intra-species chemosensory communication. The vomeronasal organ of rodents plays an important role in detecting these compounds which elicit specific, stereotypic behavior upon detection. However, other compounds that induce pheromonal responses appear to be detected by specialized cells that lie within the main olfactory system.

Outstanding questions

The use of varied approaches to study the mechanism of odorant perception in diverse organisms has facilitated the identification of the pathways and molecules involved in signal transduction. The application of molecular genetic and biochemical methods have elucidated the major components in the mammalian system and demonstrated their importance by gene disruption. In contrast, the use of behavioral genetic screens in C. elegans and other invertebrates have revealed a broader array of proteins

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Expression of various odorant-response defective (odr) genes in the entomopathogenic nematode Heterorhabditis bacteriophora (Nematoda: Heterorhabditidae)
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Majority of the nematodes are beneficial and are involved in nutrient mineralisation, soil nutrient recycling and decomposition of organic matter (Bardgett and McAlister, 1999; Wright and Coleman, 2000; van den Hoogen et al., 2019). Nematodes sense their surrounding environment through photoreception, mechanoreception, chemoreception, gustation, thermoreception and hygrosensation (Perry, 1996; Krieger and Breer, 1999; Prasad and Reed, 1999; Bargmann, 2006; Robertson and Thomas, 2006; McGaughran et al., 2013; Baiocchi et al., 2017; Shivakumara et al., 2019). In the model nematode Caenorhabditis elegans, chemoreception process materialises through 32 chemosensory neurons present in its sense organs, i.e., amphids, phasmids and inner labial organs, as well as one pair of thermosensory neurons (Ward et al., 1975; Ware et al., 1975; Bargmann, 2006).
Entomopathogenic nematodes (EPNs) exhibit complex host-seeking behaviour in soil and utilise the insect- and plant-derived odorants to locate and infect their insect hosts. The odorant response defective (odr) genes were identified in Caenorhabditis elegans through a forward genetic screen for worms defective in odour sensing. It is hypothesised that odr genes could be involved in insect host recognition by the EPNs, but no information is available on these genes or their functions in EPNs. Here, we investigated and characterised odr genes in the EPN Heterorhabditis bacteriophora. Seven orthologs of C. elegans odr genes were identified by in-silico analysis in H. bacteriophora, of which four genes (Hb-odr-2, Hb-odr-3, Hb-odr-4 and Hb-odr-10) could be amplified and cloned from the cDNA. The developmental stage-specific expression in infective juvenile (IJ), fourth stage juvenile (J4) and adult stage of H. bacteriophora showed that Hb-odr-2, Hb-odr-3 and Hb-odr-10 were up-regulated only at the IJ stage, whereas Hb-odr-10 was significantly up-regulated in all the developmental stages. Exposure to insect hemolymph resulted in high transcript accumulation of Hb-odr-3 but did not affect the expression of other Hb-odr genes. The in-situ hybridisation assays showed that Hb-odr-2 mRNA expression was localised at the region of the nerve ring while that of Hb-odr-3 in the region of pharyngointestinal valve and anterior esophagous of the IJs. Our results extend the knowledge of C. elegans odr genes to the entomopathogenic nematode H. bacteriophora. To the best of our information, this is the second investigation on the characterisation of odr genes in a parasitic nematode after the plant-parasitic species Meloidogyne incognita.
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Progressive neuronal deterioration accompanied by sensory functions decline is typically observed during aging. On the other hand, structural or functional alterations of specific sensory neurons extend lifespan in the nematode Caenorhabditis elegans. Hormesis is a phenomenon by which the body benefits from moderate stress of various kinds which at high doses are harmful. Several studies indicate that different stressors can hormetically extend lifespan in C. elegans and suggest that hormetic effects could be exploited as a strategy to slow down aging and the development of age-associated (neuronal) diseases in humans. Mitochondria play a central role in the aging process and hormetic-like bimodal dose–response effects on C. elegans lifespan have been observed following different levels of mitochondrial stress.
Here we tested the hypothesis that mitochondrial stress may hormetically extend C. elegans lifespan through subtle neuronal alterations. In support of our hypothesis we find that life-lengthening dose of mitochondrial stress reduces the functionality of a subset of ciliated sensory neurons in young animals. Notably, the same pro-longevity mitochondrial treatments rescue the sensory deficits in old animals. We also show that mitochondrial stress extends C. elegans lifespan acting in part through genes required for the functionality of those neurons. To our knowledge this is the first study describing a direct causal connection between sensory neuron dysfunction and extended longevity following mitochondrial stress. Our work supports the potential anti-aging effect of neuronal hormesis and open interesting possibility for the development of therapeutic strategy for age-associated neurodegenerative disorders.
An investigation on the chemotactic responses of different entomopathogenic nematode strains to mechanically damaged maize root volatile compounds
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Citation Excerpt :
Chemosensation and chemotaxis are essential processes in the survival of both free-living and parasitic animals. Animals rely on chemical signals in their environment to detect food sources, potential hosts, noxious compounds, reproductive partners and, occasionally, to enable them to choose between alternative developmental stages (Prasad and Reed, 1999). Chemosensation is the main sensory mode used by nematodes to orient themselves to their hosts.
Entomopathogenic nematodes (EPNs) respond to a variety of stimuli when foraging. In a laboratory investigation, we tested the chemotactic responses of 8 EPN strains (Steinernema and Heterorhabditis) to three mechanically damaged maize root compounds (linalool, α-caryophyllene and β-caryophyllene). We hypothesized that the EPN directional response to the tested volatile compounds would vary among the species and volatile compound and may be related to foraging strategies. The nematodes with an intermediate foraging strategy (Steinernema feltiae) proved to be less active in their movement toward volatile compounds in a comparison with the ambushers (Steinernema carpocapsae) and cruisers (Steinernema kraussei and Heterorhabditis bacteriophora); β-caryophyllene was found to be the most attractive substance in our experiment. The results of our investigation showed that the cruisers were more attracted to β-caryophyllene than the ambushers and intermediates. The foraging strategy did not affect the movement of the IJs toward the other tested volatile compounds or the control. Our results suggest that the response to different volatile cues is more a strain-specific characteristic than a different host-searching strategy. Only S. carpocapsae strain B49 displayed an attraction to linalool, whereas S. kraussei showed a retarded reaction to β-caryophyllene and α-caryophyllene in our experiment. The EPN strains showed only a weak attraction to α-caryophyllene, suggesting that this volatile compound could not have an important role in the orientation of IJs to the damaged roots of maize plants. These results expand our knowledge of volatile compounds as the cues that may be used by EPNs for finding hosts or other aspects of navigation in the soil.
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Citation Excerpt :
The nematode provides a genetically tractable in vivo model that is manipulated in ways not easily accomplished in mammalian systems. Taken in combination with a sophisticated repertoire of reproducible chemosensory behaviors mediated by well characterized neuronal circuits, C. elegans is an ideal system in which to identify and functionally characterize molecular mechanisms that underlie neuronal signal transduction and regulation (59, 60). In particular, the chemosensory deficit characteristic of Ce-grk-2 mutant animals allowed us to selectively disrupt Ce-GRK-2 interactions and function, thereby testing which are required for proper in vivo Ce-GRK-2 regulation of chemosensory signaling.
G protein-coupled receptor kinases (GRKs) are key regulators of signal transduction that specifically phosphorylate activated G protein-coupled receptors (GPCRs) to terminate signaling. Biochemical and crystallographic studies have provided great insight into mammalian GRK2/3 interactions and structure. However, despite extensive in vitro characterization, little is known about the in vivo contribution of these described GRK structural domains and interactions to proper GRK function in signal regulation. We took advantage of the disrupted chemosensory behavior characteristic of Caenorhabditis elegans grk-2 mutants to discern the interactions required for proper in vivo Ce-GRK-2 function. Informed by mammalian crystallographic and biochemical data, we introduced amino acid substitutions into the Ce-grk-2 coding sequence that are predicted to selectively disrupt GPCR phosphorylation, Gα_q/11 binding, Gβγ binding, or phospholipid binding. Changing the most amino-terminal residues, which have been shown in mammalian systems to be required specifically for GPCR phosphorylation but not phosphorylation of alternative substrates or recruitment to activated GPCRs, eliminated the ability of Ce-GRK-2 to restore chemosensory signaling. Disrupting interaction between the predicted Ce-GRK-2 amino-terminal α-helix and kinase domain, posited to stabilize GRKs in their active ATP- and GPCR-bound conformation, also eliminated Ce-GRK-2 chemosensory function. Finally, although changing residues within the RH domain, predicted to disrupt interaction with Gα_q/11, did not affect Ce-GRK-2 chemosensory function, disruption of the predicted PH domain-mediated interactions with Gβγ and phospholipids revealed that both contribute to Ce-GRK-2 function in vivo. Combined, we have demonstrated functional roles for broadly conserved GRK2/3 structural domains in the in vivo regulation of organismal behavior.
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Trends in Genetics

ReviewChemosensation: molecular mechanisms in worms and mammals

Abstract

Section snippets

Roles of olfaction in diverse organisms

Molecular approaches to olfactory transduction

Signaling pathways in mammals and worms

Pheromone detection in mammals

Outstanding questions

Cell

J. Steroid. Biochem. Mol. Biol.

Curr. Opin. Genet. Dev.

Cell

Cell

Neuron

FEBS Lett.

Neuron

Trends Genet.

Cell

Cell

Neuron

Neuron

Neuron

Biophys. J.

Cell

Cell

Cell

Cell

Neuron

Cell

Cell

Cell

Review
Chemosensation: molecular mechanisms in worms and mammals