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  1. Article ; Online: Multisite regulation integrates multimodal context in sensory circuits to control persistent behavioral states in C. elegans

    Saurabh Thapliyal / Isabel Beets / Dominique A. Glauser

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 19

    Abstract: Abstract 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 ... ...

    Abstract Abstract 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. elegans integrates environmental temperature and food availability over different timescales to engage in persistent dwelling, scanning, global or glocal search strategies matching thermoregulatory and feeding needs. Transition between states, in each case, involves regulating multiple processes including AFD or FLP tonic sensory neurons activity, neuropeptide expression and downstream circuit responsiveness. State-specific FLP-6 or FLP-5 neuropeptide signaling acts on a distributed set of inhibitory GPCR(s) to promote scanning or glocal search, respectively, bypassing dopamine and glutamate-dependent behavioral state control. Integration of multimodal context via multisite regulation in sensory circuits might represent a conserved regulatory logic for a flexible prioritization on the valence of multiple inputs when operating persistent behavioral state transitions.
    Keywords Science ; Q
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The FMRFamide-like peptide family in nematodes

    IsabelBeets

    Frontiers in Endocrinology, Vol

    2014  Volume 5

    Abstract: In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) ... ...

    Abstract In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) represent the largest known family of neuropeptides in invertebrates. In the phylum Nematoda, at least 32 flp genes are classified, making the FLP system of nematodes unusually complex. The diversity of the nematode FLP complement is most extensively mapped in Caenorhabditis elegans, where over 70 FLPs have been predicted. FLPs have shown to be expressed in the majority of the 302 C. elegans neurons including interneurons, sensory and motor neurons. The vast expression of FLPs is reflected in the broad functional repertoire of nematode FLP signaling, including neuroendocrine and neuromodulatory effects on locomotory activity, reproduction, feeding, and behavior. In contrast to the many identified nematode FLPs, only few peptides have been assigned a receptor and there is the need to clarify the pathway components and working mechanisms of the FLP signaling network. Here, we review the diversity, distribution, and functions of FLPs in nematodes.
    Keywords Feeding Behavior ; Reproduction ; C. elegans ; Nematodes ; Neuropeptide ; G protein-coupled receptor ; FMRFamide-like peptides (FLPs) ; Diseases of the endocrine glands. Clinical endocrinology ; RC648-665 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
    Language English
    Publishing date 2014-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Neuronal GPCR NMUR-1 regulates distinct immune responses to different pathogens

    Phillip Wibisono / Shawndra Wibisono / Jan Watteyne / Chia-Hui Chen / Durai Sellegounder / Isabel Beets / Yiyong Liu / Jingru Sun

    Cell Reports, Vol 38, Iss 6, Pp 110321- (2022)

    2022  

    Abstract: Summary: A key question in current immunology is how the innate immune system generates high levels of specificity. Using the Caenorhabditis elegans model system, we demonstrate that functional loss of NMUR-1, a neuronal G-protein-coupled receptor ... ...

    Abstract Summary: A key question in current immunology is how the innate immune system generates high levels of specificity. Using the Caenorhabditis elegans model system, we demonstrate that functional loss of NMUR-1, a neuronal G-protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans innate immunity against various bacterial pathogens. Transcriptomic analyses and functional assays reveal that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors involved in binding to RNA polymerase II regulatory regions, which, in turn, controls the expression of distinct immune genes in response to different pathogens. These results uncover a molecular basis for the specificity of C. elegans innate immunity. Given the evolutionary conservation of NMUR-1 signaling in immune regulation across multicellular organisms, our study could provide mechanistic insights into understanding the specificity of innate immunity in other animals, including mammals.
    Keywords immunological specificity ; innate immunity ; GPCR ; NMUR-1 ; C. elegans ; neural regulation ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Distinct neuropeptide-receptor modules regulate a sex-specific behavioral response to a pheromone

    Douglas K. Reilly / Emily J. McGlame / Elke Vandewyer / Annalise N. Robidoux / Caroline S. Muirhead / Haylea T. Northcott / William Joyce / Mark J. Alkema / Robert J. Gegear / Isabel Beets / Jagan Srinivasan

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 16

    Abstract: Reilly et al identify a neuropeptide-neuropeptide receptor (NP/NPR) module that is active in male but not in hermaphrodite C. elegans. Using a neuropeptide rescue paradigm, they demonstrate that receptor expression within pre-motor neurons mediates ... ...

    Abstract Reilly et al identify a neuropeptide-neuropeptide receptor (NP/NPR) module that is active in male but not in hermaphrodite C. elegans. Using a neuropeptide rescue paradigm, they demonstrate that receptor expression within pre-motor neurons mediates coordination of male-specific and core locomotor circuitries.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

    Amir Saberi / Ayana Jamal / Isabel Beets / Liliane Schoofs / Phillip A Newmark

    PLoS Biology, Vol 14, Iss 5, p e

    2016  Volume 1002457

    Abstract: Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) ...

    Abstract Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor mining, we identified 566 putative planarian GPCRs and classified them into conserved and phylum-specific subfamilies. We performed a functional screen to identify NPYR-1 as the cognate receptor for NPY-8, a neuropeptide required for sexual maturation and germ cell differentiation. Similar to NPY-8, knockdown of this receptor results in loss of differentiated germ cells and sexual maturity. NPYR-1 is expressed in neuroendocrine cells of the central nervous system and can be activated specifically by NPY-8 in cell-based assays. Additionally, we screened the complement of GPCRs with expression enriched in sexually reproducing planarians, and identified an orphan chemoreceptor family member, ophis, that controls differentiation of germline stem cells (GSCs). ophis is expressed in somatic cells of male and female gonads, as well as in accessory reproductive tissues. We have previously shown that somatic gonadal cells are required for male GSC specification and maintenance in planarians. However, ophis is not essential for GSC specification or maintenance and, therefore, defines a secondary role for planarian gonadal niche cells in promoting GSC differentiation. Our studies uncover the complement of planarian GPCRs and reveal previously unappreciated roles for these receptors in systemic and local (i.e., niche) regulation of germ cell development.
    Keywords Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2016-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Neuromedin U signaling regulates retrieval of learned salt avoidance in a C. elegans gustatory circuit

    Jan Watteyne / Katleen Peymen / Petrus Van der Auwera / Charline Borghgraef / Elke Vandewyer / Sara Van Damme / Iene Rutten / Jeroen Lammertyn / Rob Jelier / Liliane Schoofs / Isabel Beets

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 16

    Abstract: Learning and memory are regulated by neuropeptides. Here, the authors show that the neuropeptide CAPA-1 and its receptor NMUR-1 are required to retrieve learned salt avoidance in C. elegans. CAPA-1/NMUR-1 activation in AFD sensory neurons modulates ... ...

    Abstract Learning and memory are regulated by neuropeptides. Here, the authors show that the neuropeptide CAPA-1 and its receptor NMUR-1 are required to retrieve learned salt avoidance in C. elegans. CAPA-1/NMUR-1 activation in AFD sensory neurons modulates locomotor programs to express learned avoidance.
    Keywords Science ; Q
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Neuromedin U signaling regulates retrieval of learned salt avoidance in a C. elegans gustatory circuit

    Jan Watteyne / Katleen Peymen / Petrus Van der Auwera / Charline Borghgraef / Elke Vandewyer / Sara Van Damme / Iene Rutten / Jeroen Lammertyn / Rob Jelier / Liliane Schoofs / Isabel Beets

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 16

    Abstract: Learning and memory are regulated by neuropeptides. Here, the authors show that the neuropeptide CAPA-1 and its receptor NMUR-1 are required to retrieve learned salt avoidance in C. elegans. CAPA-1/NMUR-1 activation in AFD sensory neurons modulates ... ...

    Abstract Learning and memory are regulated by neuropeptides. Here, the authors show that the neuropeptide CAPA-1 and its receptor NMUR-1 are required to retrieve learned salt avoidance in C. elegans. CAPA-1/NMUR-1 activation in AFD sensory neurons modulates locomotor programs to express learned avoidance.
    Keywords Science ; Q
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Nature Portfolio
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    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: RPamide neuropeptides NLP-22 and NLP-2 act through GnRH-like receptors to promote sleep and wakefulness in C. elegans

    Petrus Van der Auwera / Lotte Frooninckx / Kristen Buscemi / Ryan T. Vance / Jan Watteyne / Olivier Mirabeau / Liesbet Temmerman / Wouter De Haes / Luca Fancsalszky / Alexander Gottschalk / David M. Raizen / Matthew D. Nelson / Liliane Schoofs / Isabel Beets

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 15

    Abstract: Abstract Sleep and wakefulness are fundamental behavioral states of which the underlying molecular principles are becoming slowly elucidated. Transitions between these states require the coordination of multiple neurochemical and modulatory systems. In ... ...

    Abstract Abstract Sleep and wakefulness are fundamental behavioral states of which the underlying molecular principles are becoming slowly elucidated. Transitions between these states require the coordination of multiple neurochemical and modulatory systems. In Caenorhabditis elegans sleep occurs during a larval transition stage called lethargus and is induced by somnogenic neuropeptides. Here, we identify two opposing neuropeptide/receptor signaling pathways: NLP-22 promotes behavioral quiescence, whereas NLP-2 promotes movement during lethargus, by signaling through gonadotropin-releasing hormone (GnRH) related receptors. Both NLP-2 and NLP-22 belong to the RPamide neuropeptide family and share sequence similarities with neuropeptides of the bilaterian GnRH, adipokinetic hormone (AKH) and corazonin family. RPamide neuropeptides dose-dependently activate the GnRH/AKH-like receptors GNRR-3 and GNRR-6 in a cellular receptor activation assay. In addition, nlp-22-induced locomotion quiescence requires the receptor gnrr-6. By contrast, wakefulness induced by nlp-2 overexpression is diminished by deletion of either gnrr-3 or gnrr-6. nlp-2 is expressed in a pair of olfactory AWA neurons and cycles with larval periodicity, as reported for nlp-22, which is expressed in RIA. Our data suggest that the somnogenic NLP-22 neuropeptide signals through GNRR-6, and that both GNRR-3 and GNRR-6 are required for the wake-promoting action of NLP-2 neuropeptides.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans.

    Ithai Rabinowitch / Patrick Laurent / Buyun Zhao / Denise Walker / Isabel Beets / Liliane Schoofs / Jihong Bai / William R Schafer / Millet Treinin

    PLoS Biology, Vol 14, Iss 1, p e

    2016  Volume 1002348

    Abstract: Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its ... ...

    Abstract Sensory loss induces cross-modal plasticity, often resulting in altered performance in remaining sensory modalities. Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity, only scant information exists about its cellular and molecular underpinnings. We found that Caenorhabditis elegans nematodes deprived of a sense of body touch exhibit various changes in behavior, associated with other unimpaired senses. We focused on one such behavioral alteration, enhanced odor sensation, and sought to reveal the neuronal and molecular mechanisms that translate mechanosensory loss into improved olfactory acuity. To this end, we analyzed in mechanosensory mutants food-dependent locomotion patterns that are associated with olfactory responses and found changes that are consistent with enhanced olfaction. The altered locomotion could be reversed in adults by optogenetic stimulation of the touch receptor (mechanosensory) neurons. Furthermore, we revealed that the enhanced odor response is related to a strengthening of inhibitory AWC→AIY synaptic transmission in the olfactory circuit. Consistently, inserting in this circuit an engineered electrical synapse that diminishes AWC inhibition of AIY counteracted the locomotion changes in touch-deficient mutants. We found that this cross-modal signaling between the mechanosensory and olfactory circuits is mediated by neuropeptides, one of which we identified as FLP-20. Our results indicate that under normal function, ongoing touch receptor neuron activation evokes FLP-20 release, suppressing synaptic communication and thus dampening odor sensation. In contrast, in the absence of mechanosensory input, FLP-20 signaling is reduced, synaptic suppression is released, and this enables enhanced olfactory acuity; these changes are long lasting and do not represent ongoing modulation, as revealed by optogenetic experiments. Our work adds to a growing literature on the roles of neuropeptides in cross-modal signaling, by showing how activity-dependent neuropeptide ...
    Keywords Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Discovery of sea urchin NGFFFamide receptor unites a bilaterian neuropeptide family

    Dean C. Semmens / Isabel Beets / Matthew L. Rowe / Liisa M. Blowes / Paola Oliveri / Maurice R. Elphick

    Open Biology, Vol 5, Iss

    2015  Volume 4

    Abstract: Neuropeptides are ancient regulators of physiology and behaviour, but reconstruction of neuropeptide evolution is often difficult owing to lack of sequence conservation. Here, we report that the receptor for the neuropeptide NGFFFamide in the sea urchin ... ...

    Abstract Neuropeptides are ancient regulators of physiology and behaviour, but reconstruction of neuropeptide evolution is often difficult owing to lack of sequence conservation. Here, we report that the receptor for the neuropeptide NGFFFamide in the sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) is an orthologue of vertebrate neuropeptide-S (NPS) receptors and crustacean cardioactive peptide (CCAP) receptors. Importantly, this has facilitated reconstruction of the evolution of two bilaterian neuropeptide signalling systems. Genes encoding the precursor of a vasopressin/oxytocin-type neuropeptide and its receptor duplicated in a common ancestor of the Bilateria. One copy of the precursor retained ancestral features, as seen in highly conserved vasopressin/oxytocin–neurophysin-type precursors. The other copy diverged, but this took different courses in protostomes and deuterostomes. In protostomes, the occurrence of a disulfide bridge in neuropeptide product(s) of the precursor was retained, as in CCAP, but with loss of the neurophysin domain. In deuterostomes, we see the opposite scenario—the neuropeptides lost the disulfide bridge, and neurophysin was retained (as in the NGFFFamide precursor) but was subsequently lost in vertebrate NPS precursors. Thus, the sea urchin NGFFFamide precursor and receptor are ‘missing links’ in the evolutionary history of neuropeptides that control ecdysis in arthropods (CCAP) and regulate anxiety in humans (NPS).
    Keywords neuropeptide ; evolution ; receptor ; neuropeptide-s ; sea urchin ; ngfffamide ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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