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Synaptic activity controls autophagic vacuole motility and function in dendrites

Macroautophagy (hereafter “autophagy”) is a lysosomal degradation pathway that is important for learning and memory, suggesting critical roles for autophagy at the neuronal synapse. Little is known, however, about the molecular details of how autophagy is regulated with synaptic activity. Here, we u...

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Autores principales: Kulkarni, Vineet Vinay, Anand, Anip, Herr, Jessica Brandt, Miranda, Christina, Vogel, Maria Chalokh, Maday, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020715/
https://www.ncbi.nlm.nih.gov/pubmed/33783472
http://dx.doi.org/10.1083/jcb.202002084
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author Kulkarni, Vineet Vinay
Anand, Anip
Herr, Jessica Brandt
Miranda, Christina
Vogel, Maria Chalokh
Maday, Sandra
author_facet Kulkarni, Vineet Vinay
Anand, Anip
Herr, Jessica Brandt
Miranda, Christina
Vogel, Maria Chalokh
Maday, Sandra
author_sort Kulkarni, Vineet Vinay
collection PubMed
description Macroautophagy (hereafter “autophagy”) is a lysosomal degradation pathway that is important for learning and memory, suggesting critical roles for autophagy at the neuronal synapse. Little is known, however, about the molecular details of how autophagy is regulated with synaptic activity. Here, we used live-cell confocal microscopy to define the autophagy pathway in primary hippocampal neurons under various paradigms of synaptic activity. We found that synaptic activity regulates the motility of autophagic vacuoles (AVs) in dendrites. Stimulation of synaptic activity dampens AV motility, whereas silencing synaptic activity induces AV motility. Activity-dependent effects on dendritic AV motility are local and reversible. Importantly, these effects are compartment specific, occurring in dendrites and not in axons. Most strikingly, synaptic activity increases the presence of degradative autolysosomes in dendrites and not in axons. On the basis of our findings, we propose a model whereby synaptic activity locally controls AV dynamics and function within dendrites that may regulate the synaptic proteome.
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spelling pubmed-80207152021-12-07 Synaptic activity controls autophagic vacuole motility and function in dendrites Kulkarni, Vineet Vinay Anand, Anip Herr, Jessica Brandt Miranda, Christina Vogel, Maria Chalokh Maday, Sandra J Cell Biol Article Macroautophagy (hereafter “autophagy”) is a lysosomal degradation pathway that is important for learning and memory, suggesting critical roles for autophagy at the neuronal synapse. Little is known, however, about the molecular details of how autophagy is regulated with synaptic activity. Here, we used live-cell confocal microscopy to define the autophagy pathway in primary hippocampal neurons under various paradigms of synaptic activity. We found that synaptic activity regulates the motility of autophagic vacuoles (AVs) in dendrites. Stimulation of synaptic activity dampens AV motility, whereas silencing synaptic activity induces AV motility. Activity-dependent effects on dendritic AV motility are local and reversible. Importantly, these effects are compartment specific, occurring in dendrites and not in axons. Most strikingly, synaptic activity increases the presence of degradative autolysosomes in dendrites and not in axons. On the basis of our findings, we propose a model whereby synaptic activity locally controls AV dynamics and function within dendrites that may regulate the synaptic proteome. Rockefeller University Press 2021-03-30 /pmc/articles/PMC8020715/ /pubmed/33783472 http://dx.doi.org/10.1083/jcb.202002084 Text en © 2021 Kulkarni et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Kulkarni, Vineet Vinay
Anand, Anip
Herr, Jessica Brandt
Miranda, Christina
Vogel, Maria Chalokh
Maday, Sandra
Synaptic activity controls autophagic vacuole motility and function in dendrites
title Synaptic activity controls autophagic vacuole motility and function in dendrites
title_full Synaptic activity controls autophagic vacuole motility and function in dendrites
title_fullStr Synaptic activity controls autophagic vacuole motility and function in dendrites
title_full_unstemmed Synaptic activity controls autophagic vacuole motility and function in dendrites
title_short Synaptic activity controls autophagic vacuole motility and function in dendrites
title_sort synaptic activity controls autophagic vacuole motility and function in dendrites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020715/
https://www.ncbi.nlm.nih.gov/pubmed/33783472
http://dx.doi.org/10.1083/jcb.202002084
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