Comprehensive Mapping of Neuropeptide Signaling Systems in the Sea Anemone Nematostella vectensis

Core Concepts

The sea anemone Nematostella vectensis possesses an extensive and diverse neuropeptide signaling system that has expanded independently from bilaterian neuropeptide systems.

Abstract

The authors conducted a large-scale analysis to map the neuropeptide signaling system in the sea anemone Nematostella vectensis. They first identified a comprehensive library of 64 neuropeptides derived from 33 precursor proteins in N. vectensis using mass spectrometry and bioinformatics. They then screened 161 N. vectensis G protein-coupled receptors (GPCRs) and identified 31 neuropeptide receptors activated by 14 different neuropeptides.
Phylogenetic analysis revealed that the N. vectensis neuropeptide GPCRs form distinct clusters separate from bilaterian neuropeptide receptors, suggesting an independent expansion of neuropeptide signaling in cnidarians. Mapping the expression of neuropeptide precursors and receptors to single-cell RNA-seq data showed extensive peptidergic networks in N. vectensis, with distinct cell types expressing unique combinations of neuropeptides and receptors.
The results demonstrate the complexity and diversity of the cnidarian neuropeptide signaling system, which has evolved independently from the bilaterian neuropeptide systems. This provides insights into the ancient origins and evolution of neuropeptide signaling in animals.

Stats

"Cnidarian genomes can encode a large number of class A GPCRs. The genome of the sea anemone Nematostella vectensis for example contains over 1000 GPCR genes."
"We could identify novel neuropeptide precursors, verify the processing of known neuropeptide precursors and refine cleavage site predictions. We used this information to prepare a list of 33 N. vectensis proneuropeptides, excluding potential isoforms of the same precursor but including 2 potential paralogs of the FLRNamide, LRWamide1, and pyrQITRFamide peptide precursors."
"In this screen, we identified 31 N. vectensis GPCRs activated mostly in the nanomolar range by peptides from 14 different precursors."

Quotes

"Cnidarian genomes can encode a large number of class A GPCRs. The genome of the sea anemone Nematostella vectensis for example contains over 1000 GPCR genes."
"We could identify novel neuropeptide precursors, verify the processing of known neuropeptide precursors and refine cleavage site predictions. We used this information to prepare a list of 33 N. vectensis proneuropeptides, excluding potential isoforms of the same precursor but including 2 potential paralogs of the FLRNamide, LRWamide1, and pyrQITRFamide peptide precursors."
"In this screen, we identified 31 N. vectensis GPCRs activated mostly in the nanomolar range by peptides from 14 different precursors."

Key Insights Distilled From

Large-scale deorphanization of Nematostella vectensis neuropeptide GPCRs supports the independent expansion of bilaterian and cnidarian peptidergic systems

by Thiel,D., Ya... at www.biorxiv.org 07-03-2023

https://www.biorxiv.org/content/10.1101/2023.07.03.547448v2

Deeper Inquiries

How do the neuropeptide signaling systems in cnidarians and bilaterians compare in terms of their functional roles and physiological impacts

In terms of functional roles and physiological impacts, neuropeptide signaling systems in cnidarians and bilaterians share some similarities but also exhibit significant differences. Both cnidarians and bilaterians use neuropeptides as signaling molecules to regulate various physiological processes such as behavior, reproduction, and stress responses. These neuropeptides act on G protein-coupled receptors (GPCRs) to initiate intracellular signaling cascades that modulate cellular functions. In both groups, neuropeptides are involved in coordinating responses to environmental stimuli, regulating growth and development, and maintaining homeostasis.
However, there are notable differences between cnidarian and bilaterian neuropeptide systems. Cnidarians possess a larger number of GPCRs compared to bilaterians, indicating a more extensive peptidergic signaling network in these organisms. The neuropeptides in cnidarians are often short amidated peptides, resembling those found in bilaterians, but with unique sequences and structures specific to cnidarians. Additionally, the expression patterns of neuropeptide precursors and receptors in cnidarians are more restricted to specific cell types, suggesting a more specialized and localized mode of neuropeptide signaling compared to the broader distribution seen in bilaterians.
Overall, while both cnidarians and bilaterians utilize neuropeptides and GPCRs for similar physiological functions, the specific neuropeptide sequences, receptor distributions, and network complexities differ between the two groups.

What are the potential evolutionary drivers that led to the independent expansion of neuropeptide signaling in cnidarians versus bilaterians

The independent expansion of neuropeptide signaling in cnidarians versus bilaterians can be attributed to several potential evolutionary drivers. One key factor is the unique environmental and ecological pressures faced by each group. Cnidarians, as early-diverging animals, have evolved in diverse marine environments with distinct challenges and opportunities compared to bilaterians. The expansion of neuropeptide signaling in cnidarians may have been driven by the need to adapt to specific ecological niches, regulate interactions with symbiotic organisms, and respond to environmental cues in the absence of complex nervous systems.
Another factor contributing to the independent expansion of neuropeptide signaling in cnidarians is the evolutionary history of these organisms. Cnidarians represent an ancient lineage with deep roots in the evolutionary tree of life, and their neuropeptide systems have likely undergone unique evolutionary trajectories separate from those of bilaterians. The presence of ancestral neuropeptide families in cnidarians, such as GLWamides, GRFamides, and PRXamides, suggests that these signaling systems have diversified and expanded independently in cnidarians over time.
Furthermore, genetic and genomic factors, including gene duplications, gene losses, and functional adaptations, may have played a role in shaping the neuropeptide signaling systems in cnidarians and bilaterians. The independent expansion of neuropeptide signaling in these two groups reflects the diverse evolutionary paths taken by different animal lineages in response to their respective environmental and physiological challenges.

Could the insights from the Nematostella neuropeptide system inform the development of new pharmacological tools or therapeutic approaches targeting neuropeptide receptors in other animals

Insights from the Nematostella neuropeptide system could have significant implications for the development of new pharmacological tools and therapeutic approaches targeting neuropeptide receptors in other animals. The comprehensive deorphanization of neuropeptide GPCRs in Nematostella provides valuable information on the ligand-receptor interactions and signaling pathways involved in cnidarian neuropeptide systems. By understanding the specific neuropeptide-receptor pairs and their physiological roles in Nematostella, researchers can gain insights into similar systems in other animals, including humans.
The identification of novel neuropeptides and their receptors in Nematostella opens up possibilities for the discovery of new drug targets and therapeutic agents. The knowledge of conserved and divergent aspects of neuropeptide signaling between cnidarians and bilaterians can inform the design of selective ligands and modulators for specific neuropeptide receptors. These insights could lead to the development of more targeted and effective pharmacological interventions for various conditions and diseases associated with neuropeptide dysregulation in humans.
Overall, the study of the Nematostella neuropeptide system not only enhances our understanding of evolutionary aspects of neuropeptide signaling but also holds promise for the advancement of pharmacology and drug discovery in the field of neuropeptide-based therapeutics.