PUBLICATION

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

Authors
Villani, A., Benjaminsen, J., Moritz, C., Henke, K., Hartmann, J., Norlin, N., Richter, K., Schieber, N.L., Franke, T., Schwab, Y., Peri, F.
ID
ZDB-PUB-190319-1
Date
2019
Source
Developmental Cell   49(1): 77-88.e7 (Journal)
Registered Authors
Henke, Katrin, Peri, Francesca, Villani, Ambra
Keywords
apoptotic cell clearance, brain development, efferocytosis, macrophage, microglia, neuronal cell death, neuronal immunity, phagocytosis, slc37a2, zebrafish
MeSH Terms
  • RAW 264.7 Cells
  • Phagocytosis/genetics
  • Antiporters/genetics*
  • Phagosomes/genetics
  • Phagosomes/ultrastructure*
  • Animals
  • Mice
  • Membrane Transport Proteins/genetics*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Microglia/metabolism*
  • Microglia/ultrastructure
  • Apoptosis/genetics
  • HeLa Cells
  • Phagocytes/ultrastructure
  • Humans
  • Macrophages/metabolism*
  • Macrophages/ultrastructure
  • Cell Compartmentation/genetics
  • Neurons/metabolism
  • Neurons/ultrastructure
(all 21)
PubMed
30880002 Full text @ Dev. Cell
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 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.
Genes / Markers
Figures
Figure Gallery (10 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hdb2TgTransgenic Insertion
    hdb6TgTransgenic Insertion
      t30301
        Point Mutation
        t30913
          Point Mutation
          zf147TgTransgenic Insertion
            zf148TgTransgenic Insertion
              zf149TgTransgenic Insertion
                zh901TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  1 - 6 of 6
                  Show
                  Fish
                  Antibodies
                  Name Type Antigen Genes Isotypes Host Organism
                  Ab1-tubg1monoclonal
                    IgG1Mouse
                    Ab2-slc37a2monoclonalMouse
                    1 - 2 of 2
                    Show
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    DsRedEFGDsRed
                    EGFPEFGEGFP
                    GAL4EFGGAL4
                    TagBFPEFGTagBFP
                    TagRFPEFGTagRFP
                    1 - 5 of 5
                    Show
                    Mapping
                    No data available