
Current Biology, Journal Year: 2024, Volume and Issue: 34(20), P. 4715 - 4728.e4
Published: Oct. 1, 2024
Highlights•Neuropeptidomic screen identified a neuropeptidase, NEP-2, and its targets•NEP-2 regulates NLP-3 neuropeptides to modulate egg-laying behavior•Expression of nep-2 in muscle, not neurons, is required for proper egg laying•Targeting NEP-2 animals with compromised (matricide) improves healthSummaryNeural communication requires both fast-acting neurotransmitters neuromodulators that function on slower timescales communicate. Endogenous bioactive peptides, often called "neuropeptides," comprise the largest most diverse class mediate crosstalk between brain peripheral tissues regulate physiology behaviors conserved across animal kingdom. Neuropeptide signaling can be terminated through receptor binding internalization or degradation by extracellular enzymes neuropeptidases. Inactivation neuropeptidases shape dynamics vivo specifying duration anatomic path travel before they are degraded. For neuropeptides, identity relevant inactivating peptidase(s) unknown. Here, we established screening platform C. elegans utilizing mass spectrometry-based peptidomics discover simultaneously profile specificity these against each more than 250 endogenous peptides. We worm ortholog mammalian peptidase neprilysin-2, demonstrated it specific including those circuit. found muscle cells signals from neurons behavior health reproductive system. Taken together, our results demonstrate peptidases, which an important node regulation neuropeptide signaling, affect impact behavior, physiology, aging.Graphical abstract
Language: Английский