Study of NIT domain‐containing chemoreceptors from two global phytopathogens and identification of NIT domains in eukaryotes

Molecular Microbiology, Journal Year: 2023, Volume and Issue: 119(6), P. 739 - 751

Published: April 25, 2023

Abstract Bacterial signal transduction systems are typically activated by the binding of molecules to receptor ligand domains (LBDs), such as NIT LBD. We report here identification domain in more than 15,000 receptors that were present 30 bacterial phyla, but also 19 eukaryotic expanding its known phylogenetic distribution. The formed part seven families either control transcription, mediate chemotaxis or regulate second messenger levels. have produced from chemoreceptors phytopathogens Pectobacterium atrosepticum (PacN) and Pseudomonas savastanoi (PscN) individual purified proteins. High‐throughput screening using compound libraries revealed a specificity for nitrate nitrite binding. Isothermal titration calorimetry experiments showed PacN‐LBD bound preferentially ( K D = 1.9 μM), whereas affinity PscN‐LBD 2.1 μM) was 22 times higher nitrate. Analytical ultracentrifugation indicated is monomeric presence absence ligands. R182A mutant PscN did not bind nitrite. This residue conserved aeruginosa chemoreceptor PA4520, which may be related failure nitrate/nitrite. magnitude P. towards significantly greater pacN deletion almost abolished responses both compounds. study highlights important role life advances our knowledge on universal nitrate/nitrite sensor module.

Language: Английский

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Large-scale deorphanization of Nematostella vectensis neuropeptide G protein-coupled receptors supports the independent expansion of bilaterian and cnidarian peptidergic systems

eLife, Journal Year: 2024, Volume and Issue: 12

Published: May 10, 2024

Neuropeptides are ancient signaling molecules in animals but only few peptide receptors known outside bilaterians. Cnidarians possess a large number of G protein-coupled (GPCRs) – the most common bilaterian neuropeptides these remain orphan with no ligands. We searched for sea anemone Nematostella vectensis and created library 64 peptides derived from 33 precursors. In large-scale pharmacological screen 161 N. GPCRs, we identified 31 specifically activated by 1 to 3 14 peptides. Mapping GPCR neuropeptide expression single-cell sequencing data revealed how cnidarian tissues extensively connected multilayer peptidergic networks. Phylogenetic analysis direct orthology systems supports independent expansion cnidarians ancestral peptide-receptor pairs.

Language: Английский

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Two distinct compartments of a ctenophore comb plate provide structural and functional integrity for the motility of giant multicilia

Current Biology, Journal Year: 2022, Volume and Issue: 32(23), P. 5144 - 5152.e6

Published: Oct. 21, 2022

Language: Английский

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Discovery and functional characterization of neuropeptides in crinoid echinoderms

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Dec. 13, 2022

Neuropeptides are one of the largest and most diverse families signaling molecules in animals and, accordingly, they regulate many physiological processes behaviors. Genome transcriptome sequencing has enabled identification genes encoding neuropeptide precursor proteins species from a growing variety taxa, including bilaterian non-bilaterian animals. Of particular interest deuterostome invertebrates such as phylum Echinodermata, which occupies phylogenetic position that facilitated reconstruction evolution systems Bilateria. However, our knowledge echinoderms is largely based on bioinformatic experimental analysis eleutherozoans-Asterozoa (starfish brittle stars) Echinozoa (sea urchins sea cucumbers). Little known about crinoids (feather stars lilies), sister clade to Eleutherozoa. Therefore, we have analyzed transcriptome/genome sequence data three feather star species, Anneissia japonica, Antedon mediterranea, Florometra serratissima, produce first comprehensive precursors crinoids. These include representatives several predicted crinoid precursors. Using A. mediterranea an model, investigated expression selected neuropeptides larvae (doliolaria), post-metamorphic pentacrinoids adults, providing new insights into cellular architecture nervous systems. Thus, using mRNA situ hybridization F-type SALMFamide transcripts were revealed previously undescribed population peptidergic cells located dorso-laterally doliolaria. Furthermore, immunohistochemistry calcitonin-type was aboral nerve center, circumoral ring oral tube feet ectoneural entoneural compartments system adults. Moreover, functional vasopressin/oxytocin-type (crinotocin), expressed brachial arms this peptide causes dose-dependent change mechanical behavior arm preparations vitro-the reported biological action crinoid. In conclusion, findings provide perspectives foundations for further exploration expression/function eleutherozoan echinoderms.

Language: Английский

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In silico analyses of the involvement of GPR55, CB1R and TRPV1: response to THC, contribution to temporal lobe epilepsy, structural modeling and updated evolution

Frontiers in Neuroinformatics, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 7, 2024

Introduction The endocannabinoid (eCB) system is named after the discovery that endogenous cannabinoids bind to same receptors as phytochemical compounds found in Cannabis. While include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), exogenous phytocannabinoids Δ-9 tetrahydrocannabinol (THC) cannabidiol (CBD). These finely tune neurotransmission following synapse activation, via retrograde signaling activates cannabinoid receptor 1 (CB1R) and/or transient potential cation channel subfamily V member (TRPV1). Recently, eCB has been linked several neurological diseases, such neuro-ocular abnormalities, pain insensitivity, migraine, epilepsy, addiction neurodevelopmental disorders. In current study, we aim to: (i) highlight a link between disorders, (ii) assess if THC exposure alters expression of eCB-related genes, (iii) identify evolutionary-conserved residues CB1R or TRPV1 light their function. Methods To address this, used bioinformatic approaches, transcriptomic (Gene Expression Omnibus), protein–protein (STRING), phylogenic (BLASTP, MEGA) structural (Phyre2, AutoDock, Vina, PyMol) analyzes. Results Using RNA sequencing datasets, did not observe any dysregulation transcripts major depressive bipolar disorder schizophrenia anterior cingulate cortex, nucleus accumbens dorsolateral striatum. Following vivo adolescent mice, GPR55 was significantly upregulated neurons from ventral tegmental area, while other involved were affected by exposure. Our results also suggest likely induces neuroinflammation vitro application on mice microglia. Significant downregulation TPRV1 occurred hippocampi which model temporal lobe epilepsy induced, confirming previous observations. addition, dysregulations observed both epileptic humans, included neuronal death. When scanning known interactions for (n = 12), branching neurophysiology, including proteins dopaminergic system. protein analyzes revealed forms clade with CB2R, distinct related paralogues sphingosine-1-phosphate, receptors, lysophosphatidic acid melanocortin receptors. As expected, conserved identified, are crucial anandamide-binding pocket seems have appeared later evolution. Similar TRPV1, activation. Conclusion study exposure, downregulated epilepsy. Caution advised when interpreting present results, employed secondary Common ancestors diverged jawless vertebrates during late Ordovician, 450 million years ago. Conserved mediate functions.

Language: Английский

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