Details:

Alternative Title:
Nature
Personal Author:
Fourgeaud, Lawrence ; Través, Paqui G. ; Tufail, Yusuf ; Leal-Bailey, Humberto ; Lew, Erin D. ; ... More +
Fourgeaud, Lawrence ; Través, Paqui G. ; Tufail, Yusuf ; Leal-Bailey, Humberto ; Lew, Erin D. ; Burrola, Patrick G. ; Callaway, Perri ; Zagórska, Anna ; Rothlin, Carla V. ; Nimmerjahn, Axel ; Lemke, Greg Less -
Description:
Microglia are damage sensors for the central nervous system (CNS), and the phagocytes responsible for routine non-inflammatory clearance of dead brain cells. Here we show that the TAM receptor tyrosine kinases Mer and Axl regulate these microglial functions. We find that adult mice deficient in microglial Mer and Axl exhibit a marked accumulation of apoptotic cells specifically in neurogenic regions of the CNS, and that microglial phagocytosis of the apoptotic cells generated during adult neurogenesis is normally driven by both TAM receptor ligands Gas6 and protein S. Using live two-photon imaging, we demonstrate that the microglial response to brain damage is also TAM-regulated, as TAM-deficient microglia display reduced process motility and delayed convergence to sites of injury. Finally, we show that microglial expression of Axl is prominently upregulated in the inflammatory environment that develops in a mouse model of Parkinson's disease. Together, these results establish TAM receptors as both controllers of microglial physiology and potential targets for therapeutic intervention in CNS disease.
Subject:
[+]
Adult Neurogenesis
Animals
Apoptosis
Apoptotic Cells
Article
Axl
Brain
Brain Injuries
Disease Models, Animal
Female
Inflammation
Intercellular Signaling Peptides And Proteins
Ligands
Male
Mer
Mice
Microglia
Neurodegeneration
Neurogenesis
Parkinson Disease
Phagocytosis
Phagoptosis
Protein S
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Signal Transduction
Stem Cell Niche
Up-Regulation
Microglia
Phagocytosis

Source:
Nature. 532(7598):240-244.
Pubmed ID:
27049947
Pubmed Central ID:
PMC5358512
Document Type:
Journal Article
Funding:
R01 NS085938/NS/NINDS NIH HHS/United States ; P30CA014195/CA/NCI NIH HHS/United States ; DP2 NS083038/NS/NINDS NIH HHS/United States ; R01 AI089824/AI/NIAID NIH HHS/United States ; Howard Hughes Medical Institute/United States ; ... More +
R01 NS085938/NS/NINDS NIH HHS/United States ; P30CA014195/CA/NCI NIH HHS/United States ; DP2 NS083038/NS/NINDS NIH HHS/United States ; R01 AI089824/AI/NIAID NIH HHS/United States ; Howard Hughes Medical Institute/United States ; DP2 NS083038/DP/NCCDPHP CDC HHS/United States ; R01 AI101400/AI/NIAID NIH HHS/United States ; R01 NS085296/NS/NINDS NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:e9fb251324cd2139c1764829e387f2c66a219a310f99f0d710817e3b71239275
File Type:

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