The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo
Abstract
Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mice revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases in order to sustain neuronal migration.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (PJT 153026)
- Armen Saghatelyan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- D Nora Abrous, Neurocentre Magendie, INSERM, France
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations of Canadian Council of Animal Care. All the experiments were approved by the Université Laval animal protection committee (#2014-178 and 2019-020).
Version history
- Received: February 13, 2020
- Accepted: September 26, 2020
- Accepted Manuscript published: September 28, 2020 (version 1)
- Version of Record published: October 14, 2020 (version 2)
Copyright
© 2020, Bressan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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