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FOXO regulates neuromuscular junction homeostasis during Drosophila aging

Allison Birnbaum, Kai Chang, Hua Bai
doi: https://doi.org/10.1101/2020.04.13.040121
Allison Birnbaum
1Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA
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  • For correspondence: abirnba1@iastate.edu hbai@iastate.edu
Kai Chang
1Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA
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Hua Bai
1Department of Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USA
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  • For correspondence: abirnba1@iastate.edu hbai@iastate.edu
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Abstract

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 p38-MAPK pathway. Interestingly, the phosphorylation of p38 and ERK were increased in the motor neuron-specific FOXO knockdown flies, suggesting FOXO acts as a suppressor of MAPK activation. Our work reveals that FOXO is a key regulator for NMJ homeostasis, and it maintains NMJ integrity by repressing MAPK signaling during aging.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 14, 2020.
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FOXO regulates neuromuscular junction homeostasis during Drosophila aging
Allison Birnbaum, Kai Chang, Hua Bai
bioRxiv 2020.04.13.040121; doi: https://doi.org/10.1101/2020.04.13.040121
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FOXO regulates neuromuscular junction homeostasis during Drosophila aging
Allison Birnbaum, Kai Chang, Hua Bai
bioRxiv 2020.04.13.040121; doi: https://doi.org/10.1101/2020.04.13.040121

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