PUBLICATION

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

Authors
Peri, F., and Nüsslein-Volhard, C.
ID
ZDB-PUB-080602-17
Date
2008
Source
Cell   133(5): 916-927 (Journal)
Registered Authors
Nüsslein-Volhard, Christiane, Peri, Francesca
Keywords
CELLBIO, DEVBIO, MOLNEURO
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Brain
  • Embryo, Nonmammalian/metabolism
  • Microglia/immunology*
  • Neurons/cytology*
  • Phagocytosis
  • Phagosomes/metabolism*
  • Vacuolar Proton-Translocating ATPases/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed
18510934 Full text @ Cell
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes