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Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons

Dendrites function as the primary sites for synaptic input and integration with impairments in dendritic arborization being associated with dysfunctional neuronal circuitry. Post-mitotic neurons require high levels of basal autophagy to clear cytotoxic materials and autophagic dysfunction under nati...

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Autores principales: Clark, Sarah G., Graybeal, Lacey L., Bhattacharjee, Shatabdi, Thomas, Caroline, Bhattacharya, Surajit, Cox, Daniel N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218061/
https://www.ncbi.nlm.nih.gov/pubmed/30395636
http://dx.doi.org/10.1371/journal.pone.0206743
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author Clark, Sarah G.
Graybeal, Lacey L.
Bhattacharjee, Shatabdi
Thomas, Caroline
Bhattacharya, Surajit
Cox, Daniel N.
author_facet Clark, Sarah G.
Graybeal, Lacey L.
Bhattacharjee, Shatabdi
Thomas, Caroline
Bhattacharya, Surajit
Cox, Daniel N.
author_sort Clark, Sarah G.
collection PubMed
description Dendrites function as the primary sites for synaptic input and integration with impairments in dendritic arborization being associated with dysfunctional neuronal circuitry. Post-mitotic neurons require high levels of basal autophagy to clear cytotoxic materials and autophagic dysfunction under native or cellular stress conditions has been linked to neuronal cell death as well as axo-dendritic degeneration. However, relatively little is known regarding the developmental role of basal autophagy in directing aspects of dendritic arborization or the mechanisms by which the autophagic machinery may be transcriptionally regulated to promote dendritic diversification. We demonstrate that autophagy-related (Atg) genes are positively regulated by the homeodomain transcription factor Cut, and that basal autophagy functions as a downstream effector pathway for Cut-mediated dendritic terminal branching in Drosophila multidendritic (md) sensory neurons. Further, loss of function analyses implicate Atg genes in promoting cell type-specific dendritic arborization and terminal branching, while gain of function studies suggest that excessive autophagy leads to dramatic reductions in dendritic complexity. We demonstrate that the Atg1 initiator kinase interacts with the dual leucine zipper kinase (DLK) pathway by negatively regulating the E3 ubiquitin ligase Highwire and positively regulating the MAPKKK Wallenda. Finally, autophagic induction partially rescues dendritic atrophy defects observed in a model of polyglutamine toxicity. Collectively, these studies implicate transcriptional control of basal autophagy in directing dendritic terminal branching and demonstrate the importance of homeostatic control of autophagic levels for dendritic arbor complexity under native or cellular stress conditions.
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spelling pubmed-62180612018-11-19 Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons Clark, Sarah G. Graybeal, Lacey L. Bhattacharjee, Shatabdi Thomas, Caroline Bhattacharya, Surajit Cox, Daniel N. PLoS One Research Article Dendrites function as the primary sites for synaptic input and integration with impairments in dendritic arborization being associated with dysfunctional neuronal circuitry. Post-mitotic neurons require high levels of basal autophagy to clear cytotoxic materials and autophagic dysfunction under native or cellular stress conditions has been linked to neuronal cell death as well as axo-dendritic degeneration. However, relatively little is known regarding the developmental role of basal autophagy in directing aspects of dendritic arborization or the mechanisms by which the autophagic machinery may be transcriptionally regulated to promote dendritic diversification. We demonstrate that autophagy-related (Atg) genes are positively regulated by the homeodomain transcription factor Cut, and that basal autophagy functions as a downstream effector pathway for Cut-mediated dendritic terminal branching in Drosophila multidendritic (md) sensory neurons. Further, loss of function analyses implicate Atg genes in promoting cell type-specific dendritic arborization and terminal branching, while gain of function studies suggest that excessive autophagy leads to dramatic reductions in dendritic complexity. We demonstrate that the Atg1 initiator kinase interacts with the dual leucine zipper kinase (DLK) pathway by negatively regulating the E3 ubiquitin ligase Highwire and positively regulating the MAPKKK Wallenda. Finally, autophagic induction partially rescues dendritic atrophy defects observed in a model of polyglutamine toxicity. Collectively, these studies implicate transcriptional control of basal autophagy in directing dendritic terminal branching and demonstrate the importance of homeostatic control of autophagic levels for dendritic arbor complexity under native or cellular stress conditions. Public Library of Science 2018-11-05 /pmc/articles/PMC6218061/ /pubmed/30395636 http://dx.doi.org/10.1371/journal.pone.0206743 Text en © 2018 Clark et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Clark, Sarah G.
Graybeal, Lacey L.
Bhattacharjee, Shatabdi
Thomas, Caroline
Bhattacharya, Surajit
Cox, Daniel N.
Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title_full Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title_fullStr Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title_full_unstemmed Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title_short Basal autophagy is required for promoting dendritic terminal branching in Drosophila sensory neurons
title_sort basal autophagy is required for promoting dendritic terminal branching in drosophila sensory neurons
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218061/
https://www.ncbi.nlm.nih.gov/pubmed/30395636
http://dx.doi.org/10.1371/journal.pone.0206743
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