N-glycan core tri-fucosylation requires Golgi α-mannosidase III activity that impacts nematode growth and behavior.

N-glycans with complex core chitobiose modifications are observed in various free-living and parasitic nematodes but are absent in mammals. Using Caenorhabditis elegans as a model, we demonstrated that the core N-acetylglucosamine (GlcNAc) residues are modified by three fucosyltransferases (FUTs), namely FUT-1, FUT-6, and FUT-8. Interestingly, FUT-6 can only fucosylate N-glycans lacking the α1,6-mannose upper arm, indicating that a specific α-mannosidase is required to generate substrates for subsequent FUT-6 activity.

Dual-Acting Nitric Oxide Donor and Phosphodiesterase Inhibitor TOP-N53 Increases Lifespan and Health Span of .

The quest for extending lifespan and promoting a healthy aging has been a longstanding pursuit in the field of aging research. The control of aging and age-related diseases by nitric oxide (NO) and cGMP signaling is a broadly conserved process from worms to human. Here we show that TOP-N53, a dual-acting NO donor and PDE5 inhibitor, can increase both lifespan and health span in .

Multisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans.

Maintaining or shifting between behavioral states according to context is essential for animals to implement fitness-promoting strategies. How the integration of internal state, past experience and sensory inputs orchestrates persistent multidimensional behavioral changes remains poorly understood. Here, we show that C.

Multiple antagonist calcium-dependent mechanisms control CaM kinase-1 subcellular localization in a thermal nociceptor.

Nociceptive habituation is a conserved process through which pain sensitivity threshold is adjusted based on past sensory experience and which may be dysregulated in human chronic pain conditions. Noxious heat habituation in involves the nuclear translocation of CaM kinase-1 (CMK-1) in the FLP thermo-nociceptors neurons, causing reduced animal heat sensitivity and avoidance responses. The phosphorylation of CMK-1 on T179 by CaM kinase kinase-1 (CKK-1) is required for nuclear entry.

Distinct clusters of human pain gene orthologs in Caenorhabditis elegans regulate thermo-nociceptive sensitivity and plasticity.

The detection and avoidance of harmful stimuli are essential animal capabilities. The molecular and cellular mechanisms controlling nociception and its plasticity are conserved, genetically controlled processes of broad biomedical interest given their relevance to understand and treat pain conditions that represent a major health burden. Recent genome-wide association studies (GWAS) have identified a rich set of polymorphisms related to different pain conditions and pointed to many human pain gene candidates, whose connection to the pain pathways is however often poorly understood.

Temperature sensing and context-dependent thermal behavior in nematodes.

As small ectotherms, whose temperature equilibrates almost instantly with that of their environment, free-living nematodes rely on their behavior for thermoregulation. Caenorhabditis elegans has been extensively used as a model to address the fundamental mechanisms involved in thermosensation and the production of temperature-dependent behaviors. Behavioral responses include avoidance of acute noxious heat or cold stimuli and thermotactic responses to innocuous temperatures to produce oriented navigation in spatial thermogradients.

Ca/CaM binding to CaMKI promotes IMA-3 importin binding and nuclear translocation in sensory neurons to control behavioral adaptation.

Sensory and behavioral plasticity are essential for animals to thrive in changing environments. As key effectors of intracellular calcium signaling, Ca/calmodulin-dependent protein kinases (CaMKs) can bridge neural activation with the many regulatory processes needed to orchestrate sensory adaptation, including by relaying signals to the nucleus. Here, we elucidate the molecular mechanism controlling the cell activation-dependent nuclear translocation of CMK-1, the ortholog of mammalian CaMKI/IV, in thermosensory neurons in vivo.

Signaling via the FLP-14/FRPR-19 neuropeptide pathway sustains nociceptive response to repeated noxious stimuli in C. elegans.

In order to thrive in constantly changing environments, animals must adaptively respond to threatening events. Noxious stimuli are not only processed according to their absolute intensity, but also to their context. Adaptation processes can cause animals to habituate at different rates and degrees in response to permanent or repeated stimuli.

PER2 mediates CREB-dependent light induction of the clock gene Per1.

Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1).

Tissue-specific DamID protocol using nanopore sequencing.

DNA adenine methylation identification (DamID) is a powerful method to determine DNA binding profiles of proteins at a genomic scale. The method leverages the fusion between a protein of interest and the Dam methyltransferase of , which methylates proximal DNA . Here, we present an optimized procedure, which was developed for tissue-specific analyses in and successfully used to footprint genes actively transcribed by RNA polymerases and to map transcription factor binding in gene regulatory regions.

Tissue-specific isoforms of the single C. elegans Ryanodine receptor gene unc-68 control specific functions.

Ryanodine receptors (RyR) are essential regulators of cellular calcium homeostasis and signaling. Vertebrate genomes contain multiple RyR gene isoforms, expressed in different tissues and executing different functions. In contrast, invertebrate genomes contain a single RyR-encoding gene and it has long been proposed that different transcripts generated by alternative splicing may diversify their functions.

Tissue-Specific Transcription Footprinting Using RNA PoI DamID (RAPID) in .

Differential gene expression across cell types underlies development and cell physiology in multicellular organisms. is a powerful, extensively used model to address these biological questions. A remaining bottleneck relates to the difficulty to obtain comprehensive tissue-specific gene transcription data, since available methods are still challenging to execute and/or require large worm populations.

A system for the high-throughput analysis of acute thermal avoidance and adaptation in .

Nociception and its plasticity are essential biological processes controlling adaptive behavioral responses in animals. These processes are also linked to different pain conditions in human and have received considerable attention, notably studies in rodent models and the use of heat-evoked withdrawal behavior assays as a readout of unpleasant experience. More recently, invertebrates have also emerged as useful complementary models, with their own set of advantages, including their amenability to genetic manipulations, the accessibility and relative simplicity of their nervous system and ethical concerns linked to animal suffering.

Specific Ion Channels Control Sensory Gain, Sensitivity, and Kinetics in a Tonic Thermonociceptor.

Pain sensation and aversive behaviors entail the activation of nociceptor neurons, whose function is largely conserved across animals. The functional heterogeneity of nociceptors and ethical concerns are challenges for their study in mammalian models. Here, we investigate the function of a single type of genetically identified C.

Identification of avoidance genes through neural pathway-specific forward optogenetics.

Understanding how the nervous system bridges sensation and behavior requires the elucidation of complex neural and molecular networks. Forward genetic approaches, such as screens conducted in C. elegans, have successfully identified genes required to process natural sensory stimuli.

Loss of CaMKI Function Disrupts Salt Aversive Learning in .

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food.

The Bright Fluorescent Protein mNeonGreen Facilitates Protein Expression Analysis .

The Green Fluorescent Protein (GFP) has been tremendously useful in investigating cell architecture, protein localization, and protein function. Recent developments in transgenesis and genome editing methods now enable working with fewer transgene copies and, consequently, with physiological expression levels. However, lower signal intensity might become a limiting factor.

Molecules empowering animals to sense and respond to temperature in changing environments.

Adapting behavior to thermal cues is essential for animal growth and survival. Indeed, each and every biological and biochemical process is profoundly affected by temperature and its extremes can cause irreversible damage. Hence, animals have developed thermotransduction mechanisms to detect and encode thermal information in the nervous system and acclimation mechanisms to finely tune their response over different timescales.

Dual Color Neural Activation and Behavior Control with Chrimson and CoChR in Caenorhabditis elegans.

By enabling a tight control of cell excitation, optogenetics is a powerful approach to study the function of neurons and neural circuits. With its transparent body, a fully mapped nervous system, easily quantifiable behaviors and many available genetic tools, Caenorhabditis elegans is an extremely well-suited model to decipher the functioning logic of the nervous system with optogenetics. Our goal was to establish an efficient dual color optogenetic system for the independent excitation of different neurons in C.

The balance between cytoplasmic and nuclear CaM kinase-1 signaling controls the operating range of noxious heat avoidance.

Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a gain-of-function allele of the cmk-1 CaMKI gene in C.

CaMKI-dependent regulation of sensory gene expression mediates experience-dependent plasticity in the operating range of a thermosensory neuron.

Sensory adaptation represents a form of experience-dependent plasticity that allows neurons to retain high sensitivity over a broad dynamic range. The mechanisms by which sensory neuron responses are altered on different timescales during adaptation are unclear. The threshold for temperature-evoked activity in the AFD thermosensory neurons (T*(AFD)) in C.

A conserved role for p48 homologs in protecting dopaminergic neurons from oxidative stress.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Both environmental and genetic factors are thought to contribute to the pathogenesis of PD. Although several genes linked to rare familial PD have been identified, endogenous risk factors for sporadic PD, which account for the majority of PD cases, remain largely unknown.

The multiplicity of alternative splicing decisions in Caenorhabditis elegans is linked to specific intronic regulatory motifs and minisatellites.

Background: Alternative splicing diversifies the pool of messenger RNA molecules encoded by individual genes. This diversity is particularly high when multiple splicing decisions cause a combinatorial arrangement of several alternate exons. We know very little on how the multiple decisions occurring during the maturation of single transcripts are coordinated and whether specific sequence elements might be involved.

How and why Caenorhabditis elegans uses distinct escape and avoidance regimes to minimize exposure to noxious heat.

Minimizing the exposure to deleterious extremes of temperature is essential for animals to avoid tissue damages. Because their body temperature equilibrates very rapidly with their surroundings, small invertebrates are particularly vulnerable to the deleterious impact of high temperatures, which jeopardizes their growth, fertility, and survival. The present article reviews recent analyses of Caenorhabditis elegans behavior in temperature gradients covering innocuous and noxious temperatures.

acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans.

Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23 and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of monepantel.