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System-wide mapping of peptide-GPCR interactions in C. elegans
Isabel Beets1, Sven Zels1, Elke Vandewyer1
1Department of Biology, KU Leuven, 3000 Leuven, Belgium.
Cell Reports
|September 1, 2023
Summary
Researchers mapped all neuropeptide-GPCR interactions in C. elegans, revealing complex signaling networks. This study uncovers 461 peptide-GPCR pairs, advancing our understanding of brain function and peptide evolution.
Area of Science:
- Neuroscience
- Genomics
- Biochemistry
Background:
- Neuropeptides and peptide hormones are crucial signaling molecules in the brain, primarily interacting with G protein-coupled receptors (GPCRs).
- The complete organization of the peptidergic network and the functions of many peptides remain poorly understood due to limited knowledge of peptide-receptor interactions and numerous orphan GPCRs.
Purpose of the Study:
- To construct a comprehensive genome-wide map of peptide-GPCR interactions in the model organism Caenorhabditis elegans.
- To identify specific peptide-receptor pairs and elucidate the complex signaling network they form.
Main Methods:
- Utilized reverse pharmacology screening across 55,384 potential interactions.
- Integrated genomic and phylogenetic analyses to study co-evolution and conservation.
Main Results:
- Identified 461 cognate peptide-GPCR couples, revealing a vast signaling network.
- Discovered specific and complex combinatorial interactions within and across peptidergic genes.
- Provided evidence for the co-evolution and conservation of at least 14 bilaterian peptidergic systems in C. elegans.
Conclusions:
- The generated peptide-GPCR interaction map provides a foundational resource for system-wide analysis of the peptidergic network.
- The findings offer insights into the evolution and functional roles of neuropeptides and their receptors.
