RESUMO
Environmental conditions experienced early in the life of an animal can result in gene expression changes later in its life history. We have previously shown that C. elegans animals that experienced the developmentally arrested and stress resistant dauer stage (postdauers) retain a cellular memory of early-life stress that manifests during adulthood as genome-wide changes in gene expression, chromatin states, and altered life history traits. One consequence of developmental reprogramming in C. elegans postdauer adults is the downregulation of osm-9 TRPV channel gene expression in the ADL chemosensory neurons resulting in reduced avoidance to a pheromone component, ascr#3. This altered response to ascr#3 requires the principal effector of the somatic nuclear RNAi pathway, the Argonaute (AGO) NRDE-3. To investigate the role of the somatic nuclear RNAi pathway in regulating the developmental reprogramming of ADL due to early-life stress, we profiled the mRNA transcriptome of control and postdauer ADL in wild-type and nrde-3 mutant adults. We found 711 differentially expressed (DE) genes between control and postdauer ADL neurons, 90% of which are dependent upon NRDE-3. Additionally, we identified a conserved sequence that is enriched in the upstream regulatory sequences of the NRDE-3-dependent differentially expressed genes. Surprisingly, 214 of the ADL DE genes are considered "germline-expressed", including 21 genes encoding the Major Sperm Proteins and two genes encoding the sperm-specific PP1 phosphatases, GSP-3 and GSP-4. Loss of function mutations in gsp-3 resulted in both aberrant avoidance and attraction behaviors. We also show that an AGO pseudogene, Y49F6A.1 (wago-11), is expressed in ADL and is required for ascr#3 avoidance. Overall, our results suggest that small RNAs and reproductive genes program the ADL mRNA transcriptome during their developmental history and highlight a nexus between neuronal and reproductive networks in calibrating animal neuroplasticity.
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Methyl ketone (MK)-ascarosides represent essential components of several pheromones in Caenorhabditis elegans, including the dauer pheromone, which triggers the stress-resistant dauer larval stage, and the male-attracting sex pheromone. Here, we identify an acyl-CoA thioesterase, ACOT-15, that is required for the biosynthesis of MK-ascarosides. We propose a model in which ACOT-15 hydrolyzes the ß-keto acyl-CoA side chain of an ascaroside intermediate during ß-oxidation, leading to decarboxylation and formation of the MK. Using comparative metabolomics, we identify additional ACOT-15-dependent metabolites, including an unusual piperidyl-modified ascaroside, reminiscent of the alkaloid pelletierine. The ß-keto acid generated by ACOT-15 likely couples to 1-piperideine to produce the piperidyl ascaroside, which is much less dauer-inducing than the dauer pheromone, asc-C6-MK (ascr#2, 1). The bacterial food provided influences production of the piperidyl ascaroside by the worm. Our work shows how the biosynthesis of MK- and piperidyl ascarosides intersect and how bacterial food may impact chemical signaling in the worm.
Assuntos
Caenorhabditis elegans , Feromônios , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimologia , Feromônios/metabolismo , Feromônios/biossíntese , Feromônios/química , Proteínas de Caenorhabditis elegans/metabolismo , Tioléster Hidrolases/metabolismoRESUMO
Pathogens generate ubiquitous selective pressures and host-pathogen interactions alter social behaviours in many animals1-4. However, very little is known about the neuronal mechanisms underlying pathogen-induced changes in social behaviour. Here we show that in adult Caenorhabditis elegans hermaphrodites, exposure to a bacterial pathogen (Pseudomonas aeruginosa) modulates sensory responses to pheromones by inducing the expression of the chemoreceptor STR-44 to promote mating. Under standard conditions, C. elegans hermaphrodites avoid a mixture of ascaroside pheromones to facilitate dispersal5-13. We find that exposure to the pathogenic Pseudomonas bacteria enables pheromone responses in AWA sensory neurons, which mediate attractive chemotaxis, to suppress the avoidance. Pathogen exposure induces str-44 expression in AWA neurons, a process regulated by a transcription factor zip-5 that also displays a pathogen-induced increase in expression in AWA. STR-44 acts as a pheromone receptor and its function in AWA neurons is required for pathogen-induced AWA pheromone response and suppression of pheromone avoidance. Furthermore, we show that C. elegans hermaphrodites, which reproduce mainly through self-fertilization, increase the rate of mating with males after pathogen exposure and that this increase requires str-44 in AWA neurons. Thus, our results uncover a causal mechanism for pathogen-induced social behaviour plasticity, which can promote genetic diversity and facilitate adaptation of the host animals.
Assuntos
Caenorhabditis elegans , Feromônios , Pseudomonas aeruginosa , Reprodução , Comportamento Sexual Animal , Animais , Feminino , Masculino , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Glicolipídeos/metabolismo , Organismos Hermafroditas/fisiologia , Feromônios/metabolismo , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , Receptores de Feromônios/metabolismo , Reprodução/fisiologia , Células Receptoras Sensoriais/metabolismoRESUMO
Chemical communication controls a wide range of behaviors via conserved signaling networks. Axon regeneration in response to injury is determined by the interaction between the extracellular environment and intrinsic growth potential. In this study, we investigated the role of chemical signaling in axon regeneration in Caenorhabditis elegans We find that the enzymes involved in ascaroside pheromone biosynthesis, ACOX-1.1, ACOX-1.2, and DAF-22, participate in axon regeneration by producing a dauer-inducing ascaroside, ascr#5. We demonstrate that the chemoreceptor genes, srg-36 and srg-37, which encode G-protein-coupled receptors for ascr#5, are required for adult-specific axon regeneration. Furthermore, the activating mutation in egl-30 encoding Gqα suppresses axon regeneration defective phenotype in acox-1.1 and srg-36 srg-37 mutants. Therefore, the ascaroside signaling system provides a unique example of a signaling molecule that regulates the regenerative pathway in the nervous system.SIGNIFICANCE STATEMENT In Caenorhabditis elegans, axon regeneration is positively regulated by the EGL-30 Gqα-JNK MAP kinase cascade. However, it remains unclear what signals activate the EGL-30 pathway in axon regeneration. Here, we show that SRG-36 and SRG-37 act as upstream G-protein-coupled receptors (GPCRs) that activate EGL-30. C. elegans secretes a family of small-molecule pheromones called ascarosides, which serve various functions in chemical signaling. SRG-36 and SRG-37 are GPCRs for the dauer-inducing ascaroside ascr#5. Consistent with this, we found that ascr#5 activates the axon regeneration pathway via SRG-36/SRG-37 and EGL-30. Thus, ascaroside signaling promotes axon regeneration by activating the GPCR-Gqα pathway.
Assuntos
Axônios/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Regeneração Nervosa/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/fisiologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Receptores Acoplados a Proteínas G/genéticaRESUMO
Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but the molecular pathways that transmit environmental cues between generations are not well understood. Here, we show that, in Caenorhabditis elegans, social cues modulate maternal provisioning to regulate gene silencing in offspring. Intergenerational signal transmission depends on a pheromone-sensing neuron and neuronal FMRFamide (Phe-Met-Arg-Phe)-like peptides. Parental FMRFamide-like peptide signaling dampens oxidative stress resistance and promotes the deposition of mRNAs for translational components in progeny, which, in turn, reduces gene silencing. This study identifies a previously unknown pathway for intergenerational communication that links neuronal responses to maternal provisioning. We suggest that loss of social cues in the parental environment represents an adverse environment that stimulates stress responses across generations.
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Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) hybrid systems typically use complex protein-protein interactions to facilitate direct transfer of intermediates between these multimodular megaenzymes. In the canal-associated neurons (CANs) of Caenorhabditis elegans, PKS-1 and NRPS-1 produce the nemamides, the only known hybrid polyketide-nonribosomal peptides biosynthesized by animals, through a poorly understood mechanism. Here, we use genome editing and mass spectrometry to map the roles of individual PKS-1 and NRPS-1 enzymatic domains in nemamide biosynthesis. Furthermore, we show that nemamide biosynthesis requires at least five additional enzymes expressed in the CANs that are encoded by genes distributed across the worm genome. We identify the roles of these enzymes and discover a mechanism for trafficking intermediates between a PKS and an NRPS. Specifically, the enzyme PKAL-1 activates an advanced polyketide intermediate as an adenylate and directly loads it onto a carrier protein in NRPS-1. This trafficking mechanism provides a means by which a PKS-NRPS system can expand its biosynthetic potential and is likely important for the regulation of nemamide biosynthesis.
Assuntos
Vias Biossintéticas/genética , Proteínas de Caenorhabditis elegans/genética , Peptídeo Sintases/genética , Peptídeos/metabolismo , Policetídeo Sintases/genética , Policetídeos/metabolismo , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Cromatografia Líquida/métodos , Enzimas/genética , Enzimas/metabolismo , Expressão Gênica , Espectrometria de Massas/métodos , Estrutura Molecular , Mutação , Neurônios/metabolismo , Peptídeo Sintases/metabolismo , Peptídeos/química , Policetídeo Sintases/metabolismo , Policetídeos/químicaRESUMO
Animals can adapt to dynamic environmental conditions by modulating their developmental programs. Understanding the genetic architecture and molecular mechanisms underlying developmental plasticity in response to changing environments is an important and emerging area of research. Here, we show a novel role of cAMP response element binding protein (CREB)-encoding crh-1 gene in developmental polyphenism of C. elegans. Under conditions that promote normal development in wild-type animals, crh-1 mutants inappropriately form transient pre-dauer (L2d) larvae and express the L2d marker gene. L2d formation in crh-1 mutants is specifically induced by the ascaroside pheromone ascr#5 (asc-ωC3; C3), and crh-1 functions autonomously in the ascr#5-sensing ASI neurons to inhibit L2d formation. Moreover, we find that CRH-1 directly binds upstream of the daf-7 TGF-ß locus and promotes its expression in the ASI neurons. Taken together, these results provide new insight into how animals alter their developmental programs in response to environmental changes.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adaptação Fisiológica/genética , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Ciclo Celular , Processos de Crescimento Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Larva/genética , Larva/crescimento & desenvolvimento , Feromônios/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologiaRESUMO
The nematode Caenorhabditis elegans produces a broad family of pheromones, known as the ascarosides, that are modified with a variety of groups derived from primary metabolism. These modifications are essential for the diverse activities of the ascarosides in development and various behaviors, including attraction, aggregation, avoidance, and foraging. The mechanism by which these different groups are added to the ascarosides is poorly understood. Here, we identify a family of over 30 enzymes, which are homologous to mammalian carboxylesterase (CES) enzymes, and show that a number of these enzymes are responsible for the selective addition of specific modifications to the ascarosides. Through stable isotope feeding experiments, we demonstrate the in vivo activity of the CES-like enzymes and provide direct evidence that the acyl-CoA synthetase ACS-7, which was previously implicated in the attachment of certain modifications to the ascarosides in C. elegans, instead activates the side chains of certain ascarosides for shortening through ß-oxidation. Our data provide a key to the combinatorial logic that gives rise to different modified ascarosides, which should greatly facilitate the exploration of the specific biological functions of these pheromones in the worm.
Assuntos
Caenorhabditis elegans/enzimologia , Carboxilesterase/metabolismo , Coenzima A Ligases/metabolismo , Animais , Glicolipídeos/biossíntese , Glicolipídeos/química , Estrutura MolecularRESUMO
Social environment modulates learning through unknown mechanisms. Here, we report that a pheromone mixture that signals overcrowding inhibits C. elegans from learning to avoid pathogenic bacteria. We find that learning depends on the balanced signaling of two insulin-like peptides (ILPs), INS-16 and INS-4, which act respectively in the pheromone-sensing neuron ADL and the bacteria-sensing neuron AWA. Pheromone exposure inhibits learning by disrupting this balance: it activates ADL and increases expression of ins-16, and this cellular effect reduces AWA activity and AWA-expressed ins-4. The activities of the sensory neurons are required for learning and the expression of the ILPs. Interestingly, pheromones also promote the ingestion of pathogenic bacteria while increasing resistance to the pathogen. Thus, the balance of the ILP signals integrates social information into the learning process as part of a coordinated adaptive response that allows consumption of harmful food during times of high population density.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Insulinas/metabolismo , Aprendizagem/fisiologia , Feromônios/metabolismo , Animais , Caenorhabditis elegans , Comportamento Alimentar/fisiologia , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/fisiologiaRESUMO
In this study, we assessed the effect of symbiotic (cognate and non-cognate) and non-symbiotic bacteria on ascaroside production of first-generation adults in two Steinernema spp.: S. carpocapsae All strain and S. feltiae SN strain. Each nematode species was reared under three bacterial scenarios: (1) cognate symbiotic, (2) non-cognate symbiotic strain and (3) non-cognate symbiotic species. Our results showed S. carpocapsae produced four quantifiable ascaroside molecules: asc-C5, asc-C6, asc-C7 and asc-C11, whereas in S. feltiae only three molecules were detected: asc-C5, asc-C7 and asc-C11. Bacterial conditions did not significantly affect the quantity of the secreted ascarosides in first-generation adults of S. carpocapsae However, in S. feltiae, Xenorhabdus nematophila All strain influenced the production of two ascaroside molecules: asc-C5 and asc-C11.
Assuntos
Feromônios/metabolismo , Rabditídios/metabolismo , Rabditídios/microbiologia , Xenorhabdus , Animais , Bactérias , Fenômenos Fisiológicos Bacterianos , Glicolipídeos/metabolismo , SimbioseRESUMO
The search for novel pheromones, hormones, and other types of natural products in the nematode Caenorhabditis elegans has accelerated over the last 10-15 years. Many of these natural products perturb fundamental processes such as developmental progression, metabolism, reproductive and somatic aging, and various behaviors and have thus become essential tools for probing these processes, which are difficult to study in higher organisms. Furthermore, given the similarity between C. elegans and parasitic nematodes, these natural products could potentially be used to manipulate the development and behavior of parasitic nematodes and target the infections caused by them.
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Produtos Biológicos/metabolismo , Caenorhabditis elegans/metabolismo , AnimaisRESUMO
Animals need to be able to alter their developmental and behavioral programs in response to changing environmental conditions. This developmental and behavioral plasticity is mainly mediated by changes in gene expression. The knowledge of the mechanisms by which environmental signals are transduced and integrated to modulate changes in sensory gene expression is limited. Exposure to ascaroside pheromone has been reported to alter the expression of a subset of putative G protein-coupled chemosensory receptor genes in the ASI chemosensory neurons of C. elegans (Kim et al., 2009; Nolan et al., 2002; Peckol et al., 1999). Here we show that ascaroside pheromone reversibly represses expression of the str-3 chemoreceptor gene in the ASI neurons. Repression of str-3 expression can be initiated only at the L1 stage, but expression is restored upon removal of ascarosides at any developmental stage. Pheromone receptors including SRBC-64/66 and SRG-36/37 are required for str-3 repression. Moreover, pheromone-mediated str-3 repression is mediated by FLP-18 neuropeptide signaling via the NPR-1 neuropeptide receptor. These results suggest that environmental signals regulate chemosensory gene expression together with internal neuropeptide signals which, in turn, modulate behavior.
Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genes de Helmintos , Neuropeptídeos/metabolismo , Feromônios/farmacologia , Receptores Odorantes/genética , Transdução de Sinais , Animais , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/genética , Mutação/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óvulo/metabolismo , Receptores de Neuropeptídeo Y , Receptores Odorantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , TemperaturaRESUMO
Caenorhabditis elegans uses aggregation pheromones to communicate its nutritional status and recruit fellow members of its species to food sources. These aggregation pheromones include the IC-ascarosides, ascarosides modified with an indole-3-carbonyl (IC) group on the 4'-position of the ascarylose sugar. Nothing is known about the biosynthesis of the IC modification beyond the fact that it is derived from tryptophan. Here, we show that C. elegans produces endogenously several indole-containing metabolites, including indole-3-pyruvic acid (IPA), indole-3-acetic acid (IAA; auxin), and indole-3-carboxylic acid, and that these metabolites are intermediates in the biosynthetic pathway from tryptophan to the IC group. Stable isotope-labeled IPA and IAA are incorporated into the IC-ascarosides. Importantly, we show that flux through the biosynthetic pathway is affected by the activity of the pyruvate dehydrogenase complex (PDC). Knockdown of the PDC by RNA interference leads to an accumulation of upstream metabolites and a reduction in downstream metabolites in the pathway. Our results show that production of aggregation pheromones is linked to PDC activity and that aggregation behavior may reflect a favorable metabolic state in the worm. Lastly, we show that treatment of C. elegans with indole-containing metabolites in the pathway induces the biosynthesis of the IC-ascarosides. Because the natural environment of C. elegans is rotting plant material, indole-containing metabolites in this environment could potentially stimulate pheromone biosynthesis and aggregation behavior in the worm. Thus, there may be important links between tryptophan metabolism in C. elegans and in plants and bacteria that enable interkingdom signaling.
Assuntos
Caenorhabditis elegans/metabolismo , Estado Nutricional , Triptofano/metabolismo , Animais , Caenorhabditis elegans/fisiologiaRESUMO
Animals change sensory responses and their eventual behaviors, depending on their internal metabolic status and external food availability. However, the mechanisms underlying feeding state-dependent behavioral changes remain undefined. Previous studies have shown that Caenorhabditis elegans hermaphrodite exhibits avoidance behaviors to acute exposure of a pheromone, ascr#3 (asc-ΔC9, C9). Here, we show that the ascr#3 avoidance behavior is modulated by feeding state via the insulin signaling pathway. Starvation increases ascr#3 avoidance behavior, and loss-of-function mutations in daf-2 insulin-like receptor gene dampen this starvation-induced ascr#3 avoidance behavior. DAF-2 and its downstream signaling molecules, including the DAF-16 FOXO transcription factor, act in the ascr#3-sensing ADL neurons to regulate synaptic transmission to downstream target neurons, including the AVA command interneurons. Moreover, we found that starvation decreases the secretion of INS-18 insulin-like peptides from the intestine, which antagonizes DAF-2 function in the ADL neurons. Altogether, this study provides insights about the molecular communication between intestine and sensory neurons delivering hunger message to sensory neurons, which regulates avoidance behavior from pheromones to facilitate survival chance.
Assuntos
Aprendizagem da Esquiva/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Insulina/metabolismo , Receptor de Insulina/metabolismo , Inanição/metabolismo , Transmissão Sináptica/fisiologia , Animais , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead/genética , Neurônios/metabolismo , Hormônios Peptídicos/metabolismo , Feromônios/metabolismo , Receptor de Insulina/genética , Transdução de Sinais , Transmissão Sináptica/genéticaRESUMO
Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for ß-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain ß-oxidation is critical for controlling the type of IC-ascarosides produced.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Glicolipídeos/biossíntese , Feromônios/biossíntese , Acil-CoA Oxidase/metabolismo , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Coenzima A Ligases/metabolismo , Glicolipídeos/química , Larva/crescimento & desenvolvimento , Larva/metabolismo , Modelos Químicos , Estrutura Molecular , Oxirredução , Feromônios/químicaRESUMO
Caenorhabditis elegans produces a complex mixture of ascaroside pheromones to control its development and behavior. Acyl-CoA oxidases, which participate in ß-oxidation cycles that shorten the side chains of the ascarosides, regulate the mixture of pheromones produced. Here, we use CRISPR-Cas9 to make specific nonsense and missense mutations in acox genes and determine the effect of these mutations on ascaroside production in vivo. Ascaroside production in acox-1.1 deletion and nonsense strains, as well as a strain with a missense mutation in a catalytic residue, confirms the central importance of ACOX-1.1 in ascaroside biosynthesis and suggests that ACOX-1.1 functions in part by facilitating the activity of other acyl-CoA oxidases. Ascaroside production in an acox-1.1 strain with a missense mutation in an ATP-binding site at the ACOX-1.1 dimer interface suggests that ATP binding is important for the enzyme to function in ascaroside biosynthesis in vivo. Ascaroside production in strains with deletion, nonsense, and missense mutations in other acox genes demonstrates that ACOX-1.1 works with ACOX-1.3 in processing ascarosides with 7-carbon side chains, ACOX-1.4 in processing ascarosides with 9- and 11-carbon side chains, and ACOX-3 in processing ascarosides with 13- and 15-carbon side chains. It also shows that ACOX-1.2, but not ACOX-1.1, processes ascarosides with 5-carbon ω-side chains. By modeling the ACOX structures, we uncover characteristics of the enzyme active sites that govern substrate preferences. Our work demonstrates the role of specific acyl-CoA oxidases in controlling the length of ascaroside side chains and thus in determining the mixture of pheromones produced by C. elegans.
Assuntos
Acil-CoA Oxidase/metabolismo , Caenorhabditis elegans/metabolismo , Feromônios/biossíntese , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Domínio Catalítico , Edição de Genes , Glicolipídeos/química , Modelos Moleculares , Mutação , OxirreduçãoRESUMO
Experiences during early development can influence neuronal functions and modulate adult behaviors [1, 2]. However, the molecular mechanisms underlying the long-term behavioral effects of these early experiences are not fully understood. The C. elegans ascr#3 (asc-ΔC9; C9) pheromone triggers avoidance behavior in adult hermaphrodites [3-7]. Here, we show that hermaphrodites that are briefly exposed to ascr#3 immediately after birth exhibit increased ascr#3-specific avoidance as adults, indicating that ascr#3-experienced animals form a long-lasting memory or imprint of this early ascr#3 exposure [8]. ascr#3 imprinting is mediated by increased synaptic activity between the ascr#3-sensing ADL neurons and their post-synaptic SMB motor neuron partners via increased expression of the odr-2 glycosylated phosphatidylinositol (GPI)-linked signaling gene in the SMB neurons. Our study suggests that the memory for early ascr#3 experience is imprinted via alteration of activity of a single synaptic connection, which in turn shapes experience-dependent plasticity in adult ascr#3 responses.
Assuntos
Caenorhabditis elegans/fisiologia , Memória , Feromônios/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Aprendizagem da Esquiva , Organismos Hermafroditas/fisiologia , Transdução de SinaisRESUMO
It is crucial for animal survival to detect dangers such as predators. A good indicator of dangers is injury of conspecifics. Here we show that fluids released from injured conspecifics invoke acute avoidance in both free-living and parasitic nematodes. Caenorhabditis elegans avoids extracts from closely related nematode species but not fruit fly larvae. The worm extracts have no impact on animal lifespan, suggesting that the worm extract may function as an alarm instead of inflicting physical harm. Avoidance of the worm extract requires the function of a cGMP signaling pathway that includes the cGMP-gated channel TAX-2/TAX-4 in the amphid sensory neurons ASI and ASK. Genetic evidence indicates that the avoidance behavior is modulated by the neurotransmitters GABA and serotonin, two common targets of anxiolytic drugs. Together, these data support a model that nematodes use a nematode-specific alarm pheromone to detect conspecific injury.
Assuntos
Caenorhabditis elegans/metabolismo , Quimiotaxia , Reação de Fuga , Feromônios/metabolismo , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Canais Iônicos/genética , Canais Iônicos/metabolismo , Feromônios/farmacologia , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
The existence of small-molecule signals that influence development in Caenorhabditis elegans has been known for several decades, but only in recent years have the chemical structures of several of these signals been established. The identification of these signals has enabled connections to be made between these small molecules and fundamental signaling pathways in C. elegans that influence not only development but also metabolism, fertility, and lifespan. Spurred by these important discoveries and aided by recent advances in comparative metabolomics and NMR spectroscopy, the field of nematode chemistry has the potential to expand dramatically in the coming years. This Perspective will focus on small-molecule pheromones and hormones that influence developmental events in the nematode life cycle (ascarosides, dafachronic acids, and nemamides), will cover more recent work regarding the biosynthesis of these signals, and will explore how the discovery of these signals is transforming our understanding of nematode development and physiology.