학술논문

Live Imaging of Neuronal Degradation by Microglia Reveals a Role for v0-ATPase a1 in Phagosomal Fusion In Vivo
Document Type
Report
Source
Cell. May 30, 2008, Vol. 133 Issue 5, p916, 12 p.
Subject
Neurons
Adenosine triphosphatase
Biological sciences
Language
English
ISSN
0092-8674
Abstract
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.04.037 Byline: Francesca Peri (1), Christiane Nusslein-Volhard (1) Keywords: CELLBIO; DEVBIO; MOLNEURO 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. Author Affiliation: (1) Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 Tubingen, Germany Article History: Received 21 June 2007; Revised 29 February 2008; Accepted 14 April 2008 Article Note: (miscellaneous) Published: May 29, 2008