TAM receptors regulate multiple features of microglial physiology

Details

• Alternative Title:
  Nature
• Personal Author:
  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
• 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.
• Subjects:
  Adult Neurogenesis Animals Apoptosis Apoptotic Cells Article Axl Axl Receptor Tyrosine Kinase Brain Brain Injuries C-Mer Tyrosine Kinase 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

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• Source:
  Nature. 532(7598):240-244
• Pubmed ID:
  27049947
• Pubmed Central ID:
  PMC5358512
• Document Type:
  Journal Article
• Funding:
  R01 NS085938/NS/NINDS NIH HHSUnited States/ ; P30CA014195/CA/NCI NIH HHSUnited States/ ; DP2 NS083038/NS/NINDS NIH HHSUnited States/ ; R01 AI089824/AI/NIAID NIH HHSUnited States/ ; HHMI/Howard Hughes Medical InstituteUnited States/ ; R01 NS110688/NS/NINDS NIH HHSUnited States/ ; DP2 NS083038/DP/NCCDPHP CDC HHSUnited States/ ; R01 AI101400/AI/NIAID NIH HHSUnited States/ ; R01 NS085296/NS/NINDS NIH HHSUnited States/ ; P30 CA014195/CA/NCI NIH HHSUnited States/
• Volume:
  532
• Issue:
  7598
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e9fb251324cd2139c1764829e387f2c66a219a310f99f0d710817e3b71239275
• Download URL:
  https://stacks.cdc.gov/view/cdc/44699/cdc_44699_DS1.pdf
• File Type:
  [PDF - 2.99 MB ]