FOXO Regulates Neuromuscular Junction Homeostasis During
FOXO
MAPK
NMJ
Rab7
aging
late endosome
p38
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2020
2020
Historique:
received:
30
05
2020
accepted:
04
12
2020
entrez:
15
2
2021
pubmed:
16
2
2021
medline:
16
2
2021
Statut:
epublish
Résumé
The transcription factor foxo is a known regulator of lifespan extension and tissue homeostasis. It has been linked to the maintenance of neuronal processes across many species and has been shown to promote youthful characteristics by regulating cytoskeletal flexibility and synaptic plasticity at the neuromuscular junction (NMJ). However, the role of foxo in aging neuromuscular junction function has yet to be determined. We profiled adult Drosophila foxo- null mutant abdominal ventral longitudinal muscles and found that young mutants exhibited morphological profiles similar to those of aged wild-type flies, such as larger bouton areas and shorter terminal branches. We also observed changes to the axonal cytoskeleton and an accumulation of late endosomes in foxo null mutants and motor neuron-specific foxo knockdown flies, similar to those of aged wild-types. Motor neuron-specific overexpression of foxo can delay age-dependent changes to NMJ morphology, suggesting foxo is responsible for maintaining NMJ integrity during aging. Through genetic screening, we identify several downstream factors mediated through foxo-regulated NMJ homeostasis, including genes involved in the MAPK pathway. Interestingly, the phosphorylation of p38 was increased in the motor neuron-specific foxo knockdown flies, suggesting foxo acts as a suppressor of p38/MAPK activation. Our work reveals that foxo is a key regulator for NMJ homeostasis, and it may maintain NMJ integrity by repressing MAPK signaling.
Identifiants
pubmed: 33584240
doi: 10.3389/fnagi.2020.567861
pmc: PMC7874159
doi:
Types de publication
Journal Article
Langues
eng
Pagination
567861Subventions
Organisme : NIA NIH HHS
ID : R00 AG048016
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG058741
Pays : United States
Informations de copyright
Copyright © 2021 Birnbaum, Sodders, Bouska, Chang, Kang, McNeill and Bai.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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