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Live Imaging of Neuronal Degradation by Microglia Reveals a Role for v0-ATPase a1 in Phagosomal Fusion In Vivo


Peri, Francesca; Nüsslein-Volhard, Christiane (2008). Live Imaging of Neuronal Degradation by Microglia Reveals a Role for v0-ATPase a1 in Phagosomal Fusion In Vivo. Cell, 133(5):916-927.

Abstract

A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly digested by microglia. Despite the importance of microglia in several neuronal pathologies, the mechanism underlying their degradation of neurons remains elusive. Here, we exploit a microglial population in the zebrafish to study this process in intact living brains. In vivo imaging reveals that digestion of neurons occurs in compartments arising from the progressive fusion of vesicles. We demonstrate that this fusion is mediated by the v0-ATPase a1 subunit. By applying live pH indicators, we show that the a1 subunit mediates fusion between phagosomes and lysosomes during phagocytosis, a function that is independent of its proton pump activity. As a real-time description of microglial phagocytosis in vivo, this work advances our understanding of microglial-mediated neuronal degeneration, a hallmark of many neuronal diseases.

Abstract

A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly digested by microglia. Despite the importance of microglia in several neuronal pathologies, the mechanism underlying their degradation of neurons remains elusive. Here, we exploit a microglial population in the zebrafish to study this process in intact living brains. In vivo imaging reveals that digestion of neurons occurs in compartments arising from the progressive fusion of vesicles. We demonstrate that this fusion is mediated by the v0-ATPase a1 subunit. By applying live pH indicators, we show that the a1 subunit mediates fusion between phagosomes and lysosomes during phagocytosis, a function that is independent of its proton pump activity. As a real-time description of microglial phagocytosis in vivo, this work advances our understanding of microglial-mediated neuronal degeneration, a hallmark of many neuronal diseases.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 May 2008
Deposited On:20 Feb 2020 07:09
Last Modified:20 Feb 2020 07:09
Publisher:Cell Press (Elsevier)
ISSN:0092-8674
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.cell.2008.04.037

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