Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair

Abstract Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their actions and their mutual interactions remains limited. Here, we demonstrate that two neuropeptide...

Full description

Saved in:
Bibliographic Details
Main Authors: Ichiro Aoki, Luca Golinelli, Eva Dunkel, Shripriya Bhat, Erschad Bassam, Isabel Beets, Alexander Gottschalk
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53899-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850179521683128320
author Ichiro Aoki
Luca Golinelli
Eva Dunkel
Shripriya Bhat
Erschad Bassam
Isabel Beets
Alexander Gottschalk
author_facet Ichiro Aoki
Luca Golinelli
Eva Dunkel
Shripriya Bhat
Erschad Bassam
Isabel Beets
Alexander Gottschalk
author_sort Ichiro Aoki
collection DOAJ
description Abstract Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their actions and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR-35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity.
format Article
id doaj-art-0ab9ffd10df04fba8cfb9c077a8e77ec
institution OA Journals
issn 2041-1723
language English
publishDate 2024-11-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-0ab9ffd10df04fba8cfb9c077a8e77ec2025-08-20T02:18:28ZengNature PortfolioNature Communications2041-17232024-11-0115111910.1038/s41467-024-53899-7Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pairIchiro Aoki0Luca Golinelli1Eva Dunkel2Shripriya Bhat3Erschad Bassam4Isabel Beets5Alexander Gottschalk6Buchmann Institute for Molecular Life Sciences, Goethe UniversityDepartment of Biology, KU LeuvenBuchmann Institute for Molecular Life Sciences, Goethe UniversityBuchmann Institute for Molecular Life Sciences, Goethe UniversityBuchmann Institute for Molecular Life Sciences, Goethe UniversityDepartment of Biology, KU LeuvenBuchmann Institute for Molecular Life Sciences, Goethe UniversityAbstract Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their actions and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR-35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity.https://doi.org/10.1038/s41467-024-53899-7
spellingShingle Ichiro Aoki
Luca Golinelli
Eva Dunkel
Shripriya Bhat
Erschad Bassam
Isabel Beets
Alexander Gottschalk
Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
Nature Communications
title Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
title_full Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
title_fullStr Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
title_full_unstemmed Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
title_short Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
title_sort hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
url https://doi.org/10.1038/s41467-024-53899-7
work_keys_str_mv AT ichiroaoki hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT lucagolinelli hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT evadunkel hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT shripriyabhat hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT erschadbassam hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT isabelbeets hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair
AT alexandergottschalk hierarchicalregulationoffunctionallyantagonisticneuropeptidesexpressedinasingleneuronpair