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

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Therapeutic Peptide Development Revolutionized: Harnessing the Power of Artificial Intelligence for Drug Discovery

Heliyon, Journal Year: 2024, Volume and Issue: 10(22), P. e40265 - e40265

Published: Nov. 1, 2024

Due to the spread of antibiotic resistance, global attention is focused on its inhibition and expansion effective medicinal compounds. The novel functional properties peptides have opened up new horizons in personalized medicine. With artificial intelligence methods combined with therapeutic peptide products, pharmaceuticals biotechnology advance drug development rapidly reduce costs. Short-chain inhibit a wide range pathogens great potential for targeting diseases. To address challenges synthesis sustainability, methods, namely machine learning, must be integrated into their production. Learning can use complicated computations select active toxic compounds metabolic activity. Through this comprehensive review, we investigated method as tool finding peptide-based drugs providing more accurate analysis through introduction predictable databases selection development.

Language: Английский

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Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior

Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Neuropeptides are abundant signaling molecules that control neuronal activity and behavior in all animals. Owing part to its well-defined compact nervous system, Caenorhabditis elegans has been one of the primary model organisms used investigate how neuropeptide networks organized these neurochemicals regulate behavior. We here review recent work expanded our understanding neuropeptidergic network C. by mapping evolutionary conservation, molecular expression, receptor–ligand interactions, system-wide organization pathways system. also describe general insights into circuit motifs spatiotemporal range peptidergic transmission have emerged from vivo studies on signaling. With efforts ongoing chart peptide other organisms, connectome can serve as a prototype further understand dynamics at organismal level.

Language: Английский

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System-wide mapping of neuropeptide-GPCR interactions inC. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 1, 2022

Summary Neuropeptides 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 and roles many neuropeptides remain elusive, as our insight into neuropeptide-receptor interactions is limited peptide GPCRs in animal models humans still orphan receptors. Here we report genome-wide neuropeptide-GPCR interaction map C. elegans . By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate peptide-GPCR couples uncover with specific complex combinatorial encoded across within single genes. These provide insights neuropeptide functions evolution. Combining dataset phylogenetic analysis supports peptide-receptor co-evolution conservation at least 14 bilaterian systems This resource lays foundation for system-wide network. Highlights System-wide deorphanizes 68 Discovery pairs additional ligands characterized show receptor Peptide-GPCR support long-range expansion

Language: Английский

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Endogenous l - to d -amino acid residue isomerization modulates selectivity between distinct neuropeptide receptor family members

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(11)

Published: March 6, 2023

The l- to d-amino acid residue isomerization of neuropeptides is an understudied post-translational modification found in animals across several phyla. Despite its physiological importance, little information available regarding the impact endogenous peptide on receptor recognition and activation. As a result, full roles play biology are not well understood. Here, we identify that Aplysia allatotropin-related (ATRP) signaling system utilizes d-residue one amino neuropeptide ligand modulate selectivity between two distinct G protein-coupled receptors (GPCRs). We first identified novel for ATRP selective D2-ATRP form, which bears single d-phenylalanine at position 2. Using cell-based activation experiments, then characterized stereoselectivity known both diastereomers, as homologous toxin peptides from carnivorous predator. displayed dual through Gαq Gαs pathways, each was selectively activated by naturally occurring diastereomer over other. Overall, our results provide insights into unexplored mechanism nature regulates intercellular communication. Given challenges detecting complex mixtures de novo identifying neuropeptides, it likely other neuropeptide-receptor systems may also utilize changes stereochemistry manner similar discovered here.

Language: Английский

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Kobayashi Award 2021: Neuropeptides, receptors, and follicle development in the ascidian, Ciona intestinalis Type A: New clues to the evolution of chordate neuropeptidergic systems from biological niches

General and Comparative Endocrinology, Journal Year: 2023, Volume and Issue: 337, P. 114262 - 114262

Published: March 15, 2023

Ciona intestinalis Type A (Ciona robusta) is a cosmopolitan species belonging to the phylum Urochordata, invertebrate chordates that are phylogenetically most closely related vertebrates. Therefore, this of interest for investigation evolution and comparative physiology endocrine, neuroendocrine, nervous systems in chordates. Our group has identified>30 neuropeptides (80% all identified ascidian neuropeptides) primarily using peptidomic approaches combined with reference genome sequences. These classified into two groups: homologs or prototypes vertebrate novel (Ciona-specific) neuropeptides. We have also cognate receptors these peptides. In particular, we elucidated multiple Ciona-specific by combination machine learning system experimental validation specific interaction predicted neuropeptide-receptor pairs, verified unprecedented phylogenies Moreover, several were found play major roles regulation ovarian follicle development. tachykinin facilitates growth vitellogenic follicles via up-regulation enzymatic activities proteases. vasopressin stimulates oocyte maturation ovulation maturation-promoting factor- matrix metalloproteinase-directed collagen degradation, respectively. cholecystokinin triggers receptor tyrosine kinase signaling subsequent activation metalloproteinase. studies revealed neuropeptidergic plays growth, maturation, Ciona, thus paving way biological evolutionary processes various

Language: Английский

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AESIS-1, a Rheumatoid Arthritis Therapeutic Peptide, Accelerates Wound Healing by Promoting Fibroblast Migration in a CXCR2-Dependent Manner

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3937 - 3937

Published: April 1, 2024

In patients with autoimmune disorders such as rheumatoid arthritis (RA), delayed wound healing is often observed. Timely and effective a crucial determinant of patient's quality life, novel materials for skin repair, bioactive peptides, are continuously being studied developed. One peptide, AESIS-1, has been its well-established anti-rheumatoid properties. this study, we attempted to use the anti-RA material AESIS-1 therapeutic wound-healing agent based on disease-modifying antirheumatic drugs (DMARDs), which can help restore prompt healing. The efficacy in was assessed using full-thickness excision model diabetic mice; studying chronic repair. Initial observations revealed that mice treated exhibited significantly advanced repair compared control group. vitro studies increased migration activity human dermal fibroblasts (HDFs) without affecting proliferative activity. Moreover, HDF cell mediated by upregulating chemokine receptor expression, CXC 2 (CXCR2). upregulation CXCR2 through treatment enhanced chemotactic reactivity ligands, including motif ligand 8 (CXCL8). directly activates ERK p38 mitogen-activated protein kinase (MAPK) signaling cascades, regulate expression fibroblasts. Our results suggest peptide strong substance increases movement turning MAPK cascades.

Language: Английский

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Affinity-Driven Aryl Diazonium Labeling of Peptide Receptors on Living Cells

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(19), P. 13676 - 13688

Published: May 2, 2024

Peptide–receptor interactions play critical roles in a wide variety of physiological processes. Methods to link bioactive peptides covalently unmodified receptors on the surfaces living cells are valuable for studying receptor signaling, dynamics, and trafficking identifying novel peptide–receptor interactions. Here, we utilize peptide analogues bearing deactivated aryl diazonium groups affinity-driven labeling receptors. We demonstrate that diazonium-bearing can label surface using both neurotensin glucagon-like 1 systems. Receptor occurs complex environment cell sequence-specific manner. further utility this covalent approach visualization by confocal fluorescence microscopy enrichment identification labeled mass spectrometry-based proteomics. Aryl diazonium-based is attractive due high abundance tyrosine histidine residues susceptible azo coupling binding sites receptors, ease incorporation into peptides, relatively small size group. This should prove be powerful general method study cellular contexts.

Language: Английский

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Impact of Machine Learning-Associated Research Strategies on the Identification of Peptide-Receptor Interactions in the Post-Omics Era

Neuroendocrinology, Journal Year: 2021, Volume and Issue: 113(2), P. 251 - 261

Published: July 26, 2021

Backgrounds: Elucidation of peptide-receptor pairs is a prerequisite for many studies in the neuroendocrine, endocrine, and neuroscience fields. Recent omics analyses have provided vast amounts peptide G protein-coupled receptor (GPCR) sequence data. GPCRs homologous peptides are easily characterized based on homology searching, relevant peptide-GPCR interactions also detected by typical signaling assays. In contrast, conventional evaluation or prediction methods, including high-throughput reverse-pharmacological assays tertiary structure-based computational analyses, not useful identifying between novel omics-derived GPCRs. Summary: Recently, an approach combining machine learning-based experimental validation predicted been shown to breakthrough this bottleneck. A learning method, logistic regression human class multiple subsequent led deorphanization orphan GPCRs, namely, identification 18 pairs. Furthermore, using another algorithm, support vector (SVM), descriptor-incorporated SVM was originally developed employed predict from closest relative vertebrates, Ciona intestinalis Type (Ciona robusta). Experimental eventually 11 Of particular interest that these newly identified displayed neither significant similarity nor molecular phylogenetic relatedness known peptides. Key Messages: These recent highlight usefulness versatility enabling efficient, reliable, systematic interactions.

Language: Английский

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Neuropeptides in psychiatry

Archives of Medicine and Health Sciences, Journal Year: 2022, Volume and Issue: 10(1), P. 59 - 67

Published: Jan. 1, 2022

In the past few decades, apprehension of human brain is on rise. There has been vast research in decades which have contributed not just to structural form, but even neuroanatomical, neurophysiological, and neurochemical correlates. terms neurochemistry, neurotransmitters already had a principal role. However, recently, attention drawn neuropeptides their role various physiological pathological effects body. The purpose present article review data general about relevance psychiatry. Our highlights findings previous studies concerning psychiatric disorders its implications as target for future treatment modalities.

Language: Английский

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