PXD050464

PXD050464 is an original dataset announced via ProteomeXchange.

Title	Neuropeptide inactivation regulates egg-laying behavior to influence reproductive health in Caenorhabditis elegans
Description	Neural communication requires both fast-acting neurotransmitters and neuromodulators that function on slower timescales to communicate. Endogenous bioactive peptides, often called “neuropeptides,” comprise the largest and most diverse class of neuromodulators that mediate crosstalk between the brain and peripheral tissues to regulate physiology and behaviors conserved across the animal kingdom. Neuropeptide signaling can be terminated through receptor binding and internalization or degradation by extracellular enzymes called neuropeptidases. Inactivation by neuropeptidases can shape the dynamics of signaling in vivo by specifying both the duration of signaling and the anatomic path neuropeptides can travel before they are degraded. For most neuropeptides, the identity of the relevant inactivating peptidase(s) is unknown. Here, we established a screening platform in C. elegans utilizing mass spectrometry-based peptidomics to discover neuropeptidases and simultaneously profile the in vivo specificity of these enzymes against each of more than 250 endogenous peptides. We identified NEP-2, a worm ortholog of the mammalian peptidase neprilysin-2, and demonstrated that it regulates specific neuropeptides, including those in the egg-laying circuit. We found that NEP-2 is required in muscle cells to regulate signals from neurons to modulate both behavior and health in the reproductive system. Taken together, our results demonstrate that peptidases, which are an important node of regulation in neuropeptide signaling, affect the dynamics of signaling to impact behavior, physiology, and aging.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:01:24.835.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050464
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jacqueline Lo
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	amidated residue; 2-pyrrolidone-5-carboxylic acid (Glu); phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-07 18:46:07	ID requested
1	2024-10-11 10:02:38	announced
⏵ 2	2024-10-22 07:01:25	announced	2024-10-22: Updated project metadata.

10.6019/PXD050464;

10.1016/J.CUB.2024.09.059;

submitter keyword: neuropeptidase,neuropeptide, healthspan, C. elegans, aging, behavior, neural circuit

Jennifer Garrison
contact affiliation	Buck Institute for Research on Aging
contact email	jgarrison@buckinstitute.org
lab head
Jacqueline Lo
contact affiliation	Buck Institute for Research on Aging
contact email	jlo@buckinstitute.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050464
     1. Label: PRIDE project
     2. Name: Neuropeptide inactivation regulates egg-laying behavior to influence reproductive health in Caenorhabditis elegans