In silico analyses of neuropeptide-like protein (NLP) profiles in parasitic nematodes

McKay, Fiona M.; McCoy, Ciaran J.; Crooks, Bethany A.; Marks, Nikki J.; Maule, Aaron G.; Atkinson, Louise E.; Mousley, Angela

doi:10.1016/j.ijpara.2021.07.002

Cited by 14 publications

(16 citation statements)

References 57 publications

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“…Likewise, we discovered two orphan receptor families related to the Drosophila trissin and CNMamide receptors (clusters 35 and 36, Data S9), suggesting that these neuropeptide systems are conserved in ecdysozoans, but trissin- and CNMamide-related peptides have not been identified in nematodes so far 130, 131 . Recently, peptidomics and comparative genomic studies also identified novel neuropeptides in C. elegans 69, 132 . Peptide discovery by these and other approaches, such as machine learning methods 40, 133 , will facilitate future deorphanizations.…”

Section: Discussionmentioning

confidence: 99%

“…Conservation of neuropeptide-receptor interactions has been shown between C. elegans and nematode parasites 142, 143 . Furthermore, peptidergic signaling regulates key aspects of nematode biology, such as reproduction, development, and locomotion 47, 132, 144, 145 . The discovery of neuropeptide-GPCR pairs in parasitic species may thus provide promising leads for the development of novel anthelminthics.…”

Section: Discussionmentioning

confidence: 99%

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

Beets¹,

Zels²,

Vandewyer³

et al. 2022

Preprint

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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 the peptidergic network and roles of many neuropeptides remain elusive, as our insight into neuropeptide-receptor interactions is limited and many peptide GPCRs in animal models and humans are still orphan receptors. Here we report a genome-wide neuropeptide-GPCR interaction map in C. elegans. By reverse pharmacology screening of over 55,384 possible interactions, we identify 461 cognate peptide-GPCR couples that uncover a broad signaling network with specific and complex combinatorial interactions encoded across and within single peptidergic genes. These interactions provide insights into neuropeptide functions and evolution. Combining our dataset with phylogenetic analysis supports peptide-receptor co-evolution and conservation of at least 14 bilaterian peptidergic systems in C. elegans. This resource lays a foundation for system-wide analysis of the peptidergic network.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Beets¹,

Zels²,

Vandewyer³

et al. 2022

Preprint

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“…Although the C. elegans nervous system is anatomically small, at the biochemical level its neuropeptide signaling pathways show similar complexity and remarkable conservation with humans and other larger-brained animals. Its genome contains 159 predicted neuropeptide precursor genes (NPP) (including 40 insulin-like peptides) that produce over 300 different neuropeptides 22, 61 . Likewise, approximately 150 C. elegans genes encode GPCRs known or predicted to be activated by neuropeptides 25, 62 .…”

Section: Introductionmentioning

confidence: 99%

The neuropeptidergic connectome ofC. elegans

Sanchez

Watteyne

Sun

et al. 2022

Preprint

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

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“…All species from this clade possess genes encoding Nemapores and GRSPs with only Romanomermis culicivorax possessing Defensin-encoding genes (see Figure 2). Clade 2/I nematodes are generally considered to be more basal and have more limited gene complements for other protein families including neuropeptides, antioxidant enzymes, G-protein-coupled receptors (GPCRs) and ATP-binding cassette transporters (ABC transporters) (McCoy et al, 2014; IHGC 2019; Xu et al, 2020; McKay et al, 2021). The reduced AMP arsenal observed in Clade 2/I may indicate that elevated AMP diversity in the Crown Clades (Clade 8-12) originated as a result of gene duplications and/or selective pressures that are not observed in the basal clades.…”

Section: Resultsmentioning

confidence: 99%

“…This reduced AMP complement was particularly evident within the Filarioidea species which may suggest that there has been a loss of AMP genes from filarial nematodes. In line with the more basal nematodes in Clade 2/I, reduced profiles of metabolic and neuropeptide pathway components are also observed in filarial nematodes (IHGC 2019;McKay et al, 2021). Filarial nematodes typically reside in the circulatory system and subcutaneous tissues of the definitive host and may, therefore, be less reliant on AMPs due to the more sterile host niches they occupy.…”

Section: Clade 2/i 8/iii and 12/iv Nematodes Possess Less Diverse Amp...mentioning

confidence: 89%

The Nematode Antimicrobial Peptidome: a novel opportunity for parasite control?

Irvine

Huws

Atkinson

et al. 2022

Preprint

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Antimicrobial Peptides (AMPs) are key constituents of the invertebrate innate immune system where they provide critical protection against microbial threat. Knowledge of AMP complements within phylum Nematoda is limited however nematodes adopt diverse life strategies and frequently reside in microbe-rich environments such that they are likely possess broad AMP profiles with bioactivity against a range of microbiota. Indeed, parasitic nematode AMPs likely have roles in defence against invading pathogens and modulation of the host microbiome. In this study the distribution and abundance of AMP-encoding genes were examined in 134 nematode genomes providing the most comprehensive profile of AMPs within phylum Nematoda. We reveal that phylum Nematoda is AMP-rich and -diverse, where 5887 genes encode AMPs. Genome and transcriptome analyses broadly reveal: (i) AMP family profiles that are influenced by nematode lifestyle where free-living nematodes appear to have an expansion of AMPs relative to parasitic species; (ii) major differences in the AMP profiles between nematode clades where Clade 9/V and 10/IV species possess expanded AMP repertoires; (iii) AMP families with highly restricted profiles (e.g. Cecropins and Diapausins) and others [e.g. Nemapores and Glycine Rich Secreted Peptides (GRSPs)] which are more widely distributed; (iv) complexity in the distribution and abundance of Defensin subfamily members; and (v) expression of AMPs in key nematode life stages. These data indicate that phylum Nematoda has a diverse array of AMPs and underscores the need to interrogate AMP function to unravel their importance to nematode biology and host-worm-microbiome interactions. Enhanced understanding of the Nematode Antimicrobial Peptidome will inform drug discovery pipelines for pathogen control.

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In silico analyses of neuropeptide-like protein (NLP) profiles in parasitic nematodes

Cited by 14 publications

References 57 publications

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

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

The neuropeptidergic connectome ofC. elegans

The Nematode Antimicrobial Peptidome: a novel opportunity for parasite control?

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