The neuropeptidergic connectome of C. elegans

Neuron, Journal Year: 2023, Volume and Issue: 111(22), P. 3570 - 3589.e5

Published: Nov. 1, 2023

Efforts are ongoing to map synaptic wiring diagrams, or connectomes, understand the neural basis of brain function. However, chemical synapses represent only one type functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles all nervous systems. By integrating single-cell anatomical gene-expression datasets with biochemical analysis receptor-ligand interactions, we have generated a draft connectome neuropeptide C. elegans system. This network characterized high connection density, extended cascades, autocrine foci, decentralized topology, large, highly interconnected core containing three constituent communities sharing similar patterns input connectivity. Intriguingly, several key hubs little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate neuropeptidergic will serve as prototype how networks neuromodulatory organized.

Language: Английский

---

System-wide mapping of peptide-GPCR interactions in C. elegans

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113058 - 113058

Published: Aug. 31, 2023

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network roles many peptides remain elusive, as our insight into peptide-receptor interactions is limited GPCRs still orphan receptors. Here we report genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate couples uncover with specific complex combinatorial encoded across within single genes. These provide insights functions evolution. Combining dataset phylogenetic analysis supports co-evolution conservation at least 14 bilaterian systems C. This resource lays foundation for system-wide network.

Language: Английский

---

Breast cancer and neurotransmitters: emerging insights on mechanisms and therapeutic directions

Oncogene, Journal Year: 2023, Volume and Issue: 42(9), P. 627 - 637

Published: Jan. 18, 2023

Exploring the relationship between various neurotransmitters and breast cancer cell growth has revealed their likely centrality to improving treatment. Neurotransmitters play a key role in biology through effects on cycle, epithelial mesenchymal transition, angiogenesis, inflammation, tumor microenvironment other pathways. receptors are vital initiation, progression drug resistance of progress our biological understanding may point way lower-cost lower-risk antitumor therapeutic strategies. This review discusses multiple context cancer. It also risk factors, repurposing pharmaceuticals impacting neurotransmitter pathways, opportunity for better integrated models that encompass exercise, intestinal microbiome, non-pharmacologic considerations. Neurotransmitters' should no longer be ignored; it appear complicate molecular picture but ubiquity wide-ranging impacts provide an organizing framework upon which further against can based.

Language: Английский

---

Mass spectrometry of short peptides reveals common features of metazoan peptidergic neurons

Nature Ecology & Evolution, Journal Year: 2022, Volume and Issue: 6(10), P. 1438 - 1448

Published: Aug. 8, 2022

Abstract The evolutionary origins of neurons remain unknown. Although recent genome data extant early-branching animals have shown that neural genes existed in the common ancestor animals, physiological and genetic properties early phase are still unclear. Here, we performed a mass spectrometry-based comprehensive survey short peptides from lineages Cnidaria, Porifera Ctenophora. We identified number mature ctenophore neuropeptides expressed associated with sensory, muscular digestive systems. stored vesicles cell bodies neurites, suggesting volume transmission similar to cnidarian bilaterian peptidergic A comparison characteristics revealed peptide-expressing cells Cnidaria Ctenophora express vast majority pivotal roles maturation, secretion degradation Bilateria. Functional analysis prediction receptors machine learning demonstrated peptide regulation wide range target effector cells, including striking parallels between neuronal Bilateria those Ctenophora, most basal neuron-bearing suggest origin metazoan nervous

Language: Английский

---

Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Jan. 6, 2023

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na

Language: Английский

---

Evolutionary conserved peptide and glycoprotein hormone-like neuroendocrine systems in C. elegans

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 584, P. 112162 - 112162

Published: Jan. 28, 2024

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication are central regulators physiology behavior in all animals. Phylogenetic analyses biochemical identifications peptide-receptor systems reveal a broad evolutionary conservation these signaling at molecular level. Substantial progress has been made recent years on characterizing physiological putative ancestral roles many peptide through comparative studies invertebrate models. Several peptides not only molecularly conserved but also have across animal phyla. Here, we focus functional insights gained nematode Caenorhabditis elegans that, with its compact well-described nervous system, provides powerful model to dissect neuroendocrine networks involved control behavior. We summarize discoveries knowledge functions hormone C. elegans.

Language: Английский

---

Regulation and physiological functions of phoenixin

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Aug. 25, 2022

Phoenixin is a newly discovered neuropeptide generated from small integral membrane protein 20. ligand for the G protein-coupled receptor 173 (GPR173) and has been detected in central peripheral tissues of human, rats, mice, bovine, zebrafish. It was initially involved regulating reproductive function by stimulating luteinizing hormone release pituitary cells increasing level gonadotropin-releasing hormone. Recently, many functions phoenixin have generalized, including regulation food intake, memory, Alzheimer’s disease, anxiety, inflammation, neuronal microglial activity, energy metabolism body fluid balance, cardiovascular function, endocrine activity. In addition, interaction between nesfatin-1 revealed. The present article summarized latest research progress on physiological phoenixin, suggesting that it potential target novel drug development clinical application.

Language: Английский

---

What is it like to be a choanoflagellate? Sensation, processing and behavior in the closest unicellular relatives of animals

Animal Cognition, Journal Year: 2023, Volume and Issue: 26(6), P. 1767 - 1782

Published: April 17, 2023

All animals evolved from a single lineage of unicellular precursors more than 600 million years ago. Thus, the biological and genetic foundations for animal sensation, cognition behavior must necessarily have arisen by modifications pre-existing features in their ancestors. Given that single-celled ancestors kingdom are extinct, only way to reconstruct how these is comparing biology genomic content extant closest living relatives. Here, we Umwelt (the subjective, perceptive world) inhabited choanoflagellates, group (or facultatively multicellular) aquatic microeukaryotes relatives animals. Although behavioral research on choanoflagellates remains patchy, existing evidence shows they capable chemosensation, photosensation mechanosensation. These processes often involve specialized sensorimotor cellular appendages (cilia, microvilli, and/or filopodia) resemble those underlie perception most sensory cells. Furthermore, comparative genomics predicts an extensive "sensory molecular toolkit" which both provides potential basis known behaviors suggests existence largely undescribed complexity presents exciting avenues future research. Finally, discuss facultative multicellularity might help us understand evolution displaced locus decision-making cell collective, new space become accessible process.

Language: Английский

---

Revisiting the evolution of Family B1 GPCRs and ligands: Insights from mollusca

Molecular and Cellular Endocrinology, Journal Year: 2024, Volume and Issue: 586, P. 112192 - 112192

Published: Feb. 24, 2024

Family B1 G protein-coupled receptors (GPCRs) are one of the most well studied neuropeptide receptor families since they play a central role in many biological processes including endocrine, gastrointestinal, cardiovascular and reproduction animals. The genes for these emerged from common ancestral gene bilaterian genomes evolved via gene/genome duplications deletions vertebrate invertebrate genomes. Their existence function have mostly been characterized vertebrates few studies exist species. Recently, an increased interest molluscs, means series become available, less modified than insect nematode genomes, ideal to explore origin evolution families. This review provides overview GPCRs their peptide ligands incorporates new data obtained Mollusca taking comparative approach challenges existing models on evolution.

Language: Английский

---

Inherency and agency in the origin and evolution of biological functions

Biological Journal of the Linnean Society, Journal Year: 2022, Volume and Issue: 139(4), P. 487 - 502

Published: Sept. 14, 2022

Abstract Although discussed by 20th century philosophers in terms drawn from the sciences of non-living systems, recent decades biological function has been considered relationship to organismal capability and purpose. Bringing two phenomena generally neglected evolutionary theory (i.e. inherency agency) bear on questions leads a rejection adaptationist ‘selected effects’ notion function. I review work showing that organisms such as placozoans can thrive with almost no functional embellishments beyond those their constituent cells physical properties simple tissues. also discuss individual tissue artificial aggregates exhibit agential behaviours are unprecedented histories respective lineages. findings unique metazoan mechanism developmental gene expression recruited, during evolution, inherent ancestral cellular functionalities into specialized cell types organs different animal groups. conclude most essential functions species which they evolved, not selected effects, many others optional ‘add-ons’, status inimical fitness-based models evolution positing traits emerge stringent cycles selection meet external challenges.

Language: Английский

---