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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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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. |
format | Online Article Text |
id | pubmed-8020715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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