A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release

Abstract The co-existence and co-transmission of neuropeptides and small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics and underlying molecular regul...

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Main Authors: Xiju Xia, Yulong Li
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56129-w
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author Xiju Xia
Yulong Li
author_facet Xiju Xia
Yulong Li
author_sort Xiju Xia
collection DOAJ
description Abstract The co-existence and co-transmission of neuropeptides and small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics and underlying molecular regulation remain poorly understood. Here, we develop a GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity and spatiotemporal resolution. Furthermore, we investigate the in vivo dynamics and molecular regulation differences between sNPF and acetylcholine (ACh) from the same neurons. Interestingly, our findings reveal distinct spatiotemporal dynamics in the release of sNPF and ACh. Notably, our results indicate that distinct synaptotagmins (Syt) are involved in these two processes, as Syt7 and Sytα for sNPF release, while Syt1 for ACh release. Thus, this high-performance GRAB sensor provides a robust tool for studying neuropeptide release and shedding insights into the unique release dynamics and molecular regulation that distinguish neuropeptides from small molecule neurotransmitters.
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spelling doaj-art-28bc729411454b8cad6cd8df8c50ff332025-01-19T12:31:06ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56129-wA high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter releaseXiju Xia0Yulong Li1State Key Laboratory of Membrane Biology, School of Life Sciences, Peking UniversityState Key Laboratory of Membrane Biology, School of Life Sciences, Peking UniversityAbstract The co-existence and co-transmission of neuropeptides and small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics and underlying molecular regulation remain poorly understood. Here, we develop a GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity and spatiotemporal resolution. Furthermore, we investigate the in vivo dynamics and molecular regulation differences between sNPF and acetylcholine (ACh) from the same neurons. Interestingly, our findings reveal distinct spatiotemporal dynamics in the release of sNPF and ACh. Notably, our results indicate that distinct synaptotagmins (Syt) are involved in these two processes, as Syt7 and Sytα for sNPF release, while Syt1 for ACh release. Thus, this high-performance GRAB sensor provides a robust tool for studying neuropeptide release and shedding insights into the unique release dynamics and molecular regulation that distinguish neuropeptides from small molecule neurotransmitters.https://doi.org/10.1038/s41467-025-56129-w
spellingShingle Xiju Xia
Yulong Li
A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
Nature Communications
title A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
title_full A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
title_fullStr A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
title_full_unstemmed A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
title_short A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
title_sort high performance grab sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release
url https://doi.org/10.1038/s41467-025-56129-w
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