Apr 14, 2020

FOXO regulates neuromuscular junction homeostasis during Drosophila aging

BioRxiv : the Preprint Server for Biology
Allison BirnbaumH. Bai

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 p3...Continue Reading

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Mentioned in this Paper

Phosphatidylinositols
TIAM1 Protein
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Chagas Disease Pathway
Triazoles
Adverse Effects
Persons
Cardiovascular Diseases
Docking -molecular Interaction
Cell Proliferation

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