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Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell

Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the...

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Autores principales: Wang, Yu, Arnold, Meghan Lee, Smart, Anna Joelle, Wang, Guoqiang, Androwski, Rebecca J, Morera, Andres, Nguyen, Ken CQ, Schweinsberg, Peter J, Bai, Ge, Cooper, Jason, Hall, David H, Driscoll, Monica, Grant, Barth D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023159/
https://www.ncbi.nlm.nih.gov/pubmed/36861960
http://dx.doi.org/10.7554/eLife.82227
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author Wang, Yu
Arnold, Meghan Lee
Smart, Anna Joelle
Wang, Guoqiang
Androwski, Rebecca J
Morera, Andres
Nguyen, Ken CQ
Schweinsberg, Peter J
Bai, Ge
Cooper, Jason
Hall, David H
Driscoll, Monica
Grant, Barth D
author_facet Wang, Yu
Arnold, Meghan Lee
Smart, Anna Joelle
Wang, Guoqiang
Androwski, Rebecca J
Morera, Andres
Nguyen, Ken CQ
Schweinsberg, Peter J
Bai, Ge
Cooper, Jason
Hall, David H
Driscoll, Monica
Grant, Barth D
author_sort Wang, Yu
collection PubMed
description Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.
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spelling pubmed-100231592023-03-18 Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell Wang, Yu Arnold, Meghan Lee Smart, Anna Joelle Wang, Guoqiang Androwski, Rebecca J Morera, Andres Nguyen, Ken CQ Schweinsberg, Peter J Bai, Ge Cooper, Jason Hall, David H Driscoll, Monica Grant, Barth D eLife Cell Biology Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease. eLife Sciences Publications, Ltd 2023-03-02 /pmc/articles/PMC10023159/ /pubmed/36861960 http://dx.doi.org/10.7554/eLife.82227 Text en © 2023, Wang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Wang, Yu
Arnold, Meghan Lee
Smart, Anna Joelle
Wang, Guoqiang
Androwski, Rebecca J
Morera, Andres
Nguyen, Ken CQ
Schweinsberg, Peter J
Bai, Ge
Cooper, Jason
Hall, David H
Driscoll, Monica
Grant, Barth D
Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title_full Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title_fullStr Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title_full_unstemmed Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title_short Large vesicle extrusions from C. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
title_sort large vesicle extrusions from c. elegans neurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023159/
https://www.ncbi.nlm.nih.gov/pubmed/36861960
http://dx.doi.org/10.7554/eLife.82227
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