| RRC ID |
51542
|
| 著者 |
E L, Zhou T, Koh S, Chuang M, Sharma R, Pujol N, Chisholm AD, Eroglu C, Matsunami H, Yan D.
|
| タイトル |
An Antimicrobial Peptide and Its Neuronal Receptor Regulate Dendrite Degeneration in Aging and Infection.
|
| ジャーナル |
Neuron
|
| Abstract |
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.
|
| 巻・号 |
97(1)
|
| ページ |
125-138.e5
|
| 公開日 |
2018-1-3
|
| DOI |
10.1016/j.neuron.2017.12.001
|
| PII |
S0896-6273(17)31124-8
|
| PMID |
29301098
|
| PMC |
PMC5757245
|
| MeSH |
Aging / immunology
Aging / metabolism*
Aging / pathology
Animals
Antimicrobial Cationic Peptides / metabolism*
Autophagy / physiology
Caenorhabditis elegans
Dendrites / metabolism
Dendrites / pathology*
Mycoses / immunology
Mycoses / pathology
Nerve Degeneration / immunology
Nerve Degeneration / metabolism*
Rats
Receptors, G-Protein-Coupled / metabolism
|
| IF |
14.415
|
| 引用数 |
9
|
| リソース情報 |
| 線虫 |
tm1498
tm1931 |
