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Clearance by Microglia Depends on Packaging of Phagosomes into a Unique Cellular Compartment

Villani, Ambra ; Benjaminsen, Jørgen ; Moritz, Christian ; Henke, Katrin ; Hartmann, Jonas ; Norlin, Nils LU ; Richter, Kerstin ; Schieber, Nicole L ; Franke, Tilman and Schwab, Yannick , et al. (2019) In Developmental Cell 49(1). p.7-88
Abstract

Phagocytic immune cells such as microglia can engulf and process pathogens and dying cells with high efficiency while still maintaining their dynamic behavior and morphology. Effective intracellular processing of ingested cells is likely to be crucial for microglial function, but the underlying cellular mechanisms are poorly understood. Using both living fish embryos and mammalian macrophages, we show that processing depends on the shrinkage and packaging of phagosomes into a unique cellular compartment, the gastrosome, with distinct molecular and ultra-structural characteristics. Loss of the transporter Slc37a2 blocks phagosomal shrinkage, resulting in the expansion of the gastrosome and the dramatic bloating of the cell. This, in... (More)

Phagocytic immune cells such as microglia can engulf and process pathogens and dying cells with high efficiency while still maintaining their dynamic behavior and morphology. Effective intracellular processing of ingested cells is likely to be crucial for microglial function, but the underlying cellular mechanisms are poorly understood. Using both living fish embryos and mammalian macrophages, we show that processing depends on the shrinkage and packaging of phagosomes into a unique cellular compartment, the gastrosome, with distinct molecular and ultra-structural characteristics. Loss of the transporter Slc37a2 blocks phagosomal shrinkage, resulting in the expansion of the gastrosome and the dramatic bloating of the cell. This, in turn, affects the ability of microglia to phagocytose and migrate toward brain injuries. Thus, this work identifies a conserved crucial step in the phagocytic pathway of immune cells and provides a potential entry point for manipulating their behavior in development and disease.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Antiporters/genetics, Apoptosis/genetics, Cell Compartmentation/genetics, HeLa Cells, Humans, Macrophages/metabolism, Membrane Transport Proteins/genetics, Mice, Microglia/metabolism, Neurons/metabolism, Phagocytes/ultrastructure, Phagocytosis/genetics, Phagosomes/genetics, RAW 264.7 Cells, Zebrafish/genetics
in
Developmental Cell
volume
49
issue
1
pages
7 - 88
publisher
Cell Press
external identifiers
  • pmid:30880002
  • scopus:85063715448
ISSN
1534-5807
DOI
10.1016/j.devcel.2019.02.014
language
English
LU publication?
no
additional info
Copyright © 2019 Elsevier Inc. All rights reserved.
id
db482a63-6b59-446a-900a-8589be087993
date added to LUP
2020-09-09 18:31:21
date last changed
2024-04-17 16:08:22
@article{db482a63-6b59-446a-900a-8589be087993,
  abstract     = {{<p>Phagocytic immune cells such as microglia can engulf and process pathogens and dying cells with high efficiency while still maintaining their dynamic behavior and morphology. Effective intracellular processing of ingested cells is likely to be crucial for microglial function, but the underlying cellular mechanisms are poorly understood. Using both living fish embryos and mammalian macrophages, we show that processing depends on the shrinkage and packaging of phagosomes into a unique cellular compartment, the gastrosome, with distinct molecular and ultra-structural characteristics. Loss of the transporter Slc37a2 blocks phagosomal shrinkage, resulting in the expansion of the gastrosome and the dramatic bloating of the cell. This, in turn, affects the ability of microglia to phagocytose and migrate toward brain injuries. Thus, this work identifies a conserved crucial step in the phagocytic pathway of immune cells and provides a potential entry point for manipulating their behavior in development and disease.</p>}},
  author       = {{Villani, Ambra and Benjaminsen, Jørgen and Moritz, Christian and Henke, Katrin and Hartmann, Jonas and Norlin, Nils and Richter, Kerstin and Schieber, Nicole L and Franke, Tilman and Schwab, Yannick and Peri, Francesca}},
  issn         = {{1534-5807}},
  keywords     = {{Animals; Antiporters/genetics; Apoptosis/genetics; Cell Compartmentation/genetics; HeLa Cells; Humans; Macrophages/metabolism; Membrane Transport Proteins/genetics; Mice; Microglia/metabolism; Neurons/metabolism; Phagocytes/ultrastructure; Phagocytosis/genetics; Phagosomes/genetics; RAW 264.7 Cells; Zebrafish/genetics}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  pages        = {{7--88}},
  publisher    = {{Cell Press}},
  series       = {{Developmental Cell}},
  title        = {{Clearance by Microglia Depends on Packaging of Phagosomes into a Unique Cellular Compartment}},
  url          = {{http://dx.doi.org/10.1016/j.devcel.2019.02.014}},
  doi          = {{10.1016/j.devcel.2019.02.014}},
  volume       = {{49}},
  year         = {{2019}},
}