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Homeostatic scaling of active zone scaffolds maintains global synaptic strength
Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated Drosophila endophilin (endo) mutants. Although active zone (AZ) number is doubled in endo mutants, a compensatory reduction in their siz...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504899/ https://www.ncbi.nlm.nih.gov/pubmed/30914419 http://dx.doi.org/10.1083/jcb.201807165 |
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author | Goel, Pragya Dufour Bergeron, Dominique Böhme, Mathias A. Nunnelly, Luke Lehmann, Martin Buser, Christopher Walter, Alexander M. Sigrist, Stephan J. Dickman, Dion |
author_facet | Goel, Pragya Dufour Bergeron, Dominique Böhme, Mathias A. Nunnelly, Luke Lehmann, Martin Buser, Christopher Walter, Alexander M. Sigrist, Stephan J. Dickman, Dion |
author_sort | Goel, Pragya |
collection | PubMed |
description | Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated Drosophila endophilin (endo) mutants. Although active zone (AZ) number is doubled in endo mutants, a compensatory reduction in their size homeostatically adjusts global neurotransmitter output to maintain synaptic strength. We find an inverse adaptation in rab3 mutants. Additional analyses using confocal, STED, and electron microscopy reveal a stoichiometric tuning of AZ scaffolds and nanoarchitecture. Axonal transport of synaptic cargo via the lysosomal kinesin adapter Arl8 regulates AZ abundance to modulate global synaptic output and sustain the homeostatic potentiation of neurotransmission. Finally, we find that this AZ scaling can interface with two independent homeostats, depression and potentiation, to remodel AZ structure and function, demonstrating a robust balancing of separate homeostatic adaptations. Thus, AZs are pliable substrates with elastic and modular nanostructures that can be dynamically sculpted to stabilize and tune both local and global synaptic strength. |
format | Online Article Text |
id | pubmed-6504899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-65048992019-11-06 Homeostatic scaling of active zone scaffolds maintains global synaptic strength Goel, Pragya Dufour Bergeron, Dominique Böhme, Mathias A. Nunnelly, Luke Lehmann, Martin Buser, Christopher Walter, Alexander M. Sigrist, Stephan J. Dickman, Dion J Cell Biol Research Articles Synaptic terminals grow and retract throughout life, yet synaptic strength is maintained within stable physiological ranges. To study this process, we investigated Drosophila endophilin (endo) mutants. Although active zone (AZ) number is doubled in endo mutants, a compensatory reduction in their size homeostatically adjusts global neurotransmitter output to maintain synaptic strength. We find an inverse adaptation in rab3 mutants. Additional analyses using confocal, STED, and electron microscopy reveal a stoichiometric tuning of AZ scaffolds and nanoarchitecture. Axonal transport of synaptic cargo via the lysosomal kinesin adapter Arl8 regulates AZ abundance to modulate global synaptic output and sustain the homeostatic potentiation of neurotransmission. Finally, we find that this AZ scaling can interface with two independent homeostats, depression and potentiation, to remodel AZ structure and function, demonstrating a robust balancing of separate homeostatic adaptations. Thus, AZs are pliable substrates with elastic and modular nanostructures that can be dynamically sculpted to stabilize and tune both local and global synaptic strength. Rockefeller University Press 2019-05-06 2019-03-26 /pmc/articles/PMC6504899/ /pubmed/30914419 http://dx.doi.org/10.1083/jcb.201807165 Text en © 2019 Goel 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 | Research Articles Goel, Pragya Dufour Bergeron, Dominique Böhme, Mathias A. Nunnelly, Luke Lehmann, Martin Buser, Christopher Walter, Alexander M. Sigrist, Stephan J. Dickman, Dion Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title | Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title_full | Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title_fullStr | Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title_full_unstemmed | Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title_short | Homeostatic scaling of active zone scaffolds maintains global synaptic strength |
title_sort | homeostatic scaling of active zone scaffolds maintains global synaptic strength |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504899/ https://www.ncbi.nlm.nih.gov/pubmed/30914419 http://dx.doi.org/10.1083/jcb.201807165 |
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