An Antimicrobial Peptide and Its Neuronal Receptor Regulate Dendrite Degeneration in Aging and Infection.
Journal Article (Journal Article)
Infections have been identified as possible risk factors for aging-related neurodegenerative diseases, but it remains unclear whether infection-related immune molecules have a causative role in neurodegeneration during aging. Here, we reveal an unexpected role of an epidermally expressed antimicrobial peptide, NLP-29 (neuropeptide-like protein 29), in triggering aging-associated dendrite degeneration in C. elegans. The age-dependent increase of nlp-29 expression is regulated by the epidermal tir-1/SARM-pmk-1/p38 MAPK innate immunity pathway. We further identify an orphan G protein-coupled receptor NPR-12 (neuropeptide receptor 12) acting in neurons as a receptor for NLP-29 and demonstrate that the autophagic machinery is involved cell autonomously downstream of NPR-12 to transduce degeneration signals. Finally, we show that fungal infections cause dendrite degeneration using a similar mechanism as in aging, through NLP-29, NPR-12, and autophagy. Our findings reveal an important causative role of antimicrobial peptides, their neuronal receptors, and the autophagy pathway in aging- and infection-associated dendrite degeneration.
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Duke Authors
Cited Authors
- E, L; Zhou, T; Koh, S; Chuang, M; Sharma, R; Pujol, N; Chisholm, AD; Eroglu, C; Matsunami, H; Yan, D
Published Date
- January 3, 2018
Published In
Volume / Issue
- 97 / 1
Start / End Page
- 125 - 138.e5
PubMed ID
- 29301098
Pubmed Central ID
- PMC5757245
Electronic International Standard Serial Number (EISSN)
- 1097-4199
Digital Object Identifier (DOI)
- 10.1016/j.neuron.2017.12.001
Language
- eng
Conference Location
- United States