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

Published version
Repository DOI

Type
Article
Change log
Authors
Beets, Isabel 
Zels, Sven 
Vandewyer, Elke 
Demeulemeester, Jonas 
Caers, Jelle 
Abstract

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 the peptidergic network and roles of many peptides remain elusive, as our insight into peptide-receptor interactions is limited and many peptide GPCRs are still orphan receptors. Here we report a genome-wide peptide-GPCR interaction map in Caenorhabditis 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 peptide 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.

Description
Keywords
C. elegans, CP: Cell biology, CP: Neuroscience, GPCR, interactome, neuropeptide, reverse pharmacology, Animals, Caenorhabditis elegans, Phylogeny, Neuropeptides, Receptors, G-Protein-Coupled, Peptide Hormones
Journal Title
Cell Rep
Conference Name
Journal ISSN
2211-1247
2211-1247
Volume Title
42
Publisher
Elsevier BV
Sponsorship
MQ: Transforming Mental Health (MQ17-24 Vertes)