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TAM receptors regulate multiple features of microglial physiology

Lawrence Fourgeaud1, Paqui G Través1, Yusuf Tufail2

  • 1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.

Nature
|April 7, 2016
PubMed

Insights

Microglia use TAM receptors Mer and Axl to clear dead cells and respond to brain injury. Deficiencies in these receptors impair microglial function, impacting neurogenesis and injury response in the CNS.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia act as CNS damage sensors and phagocytes, clearing cellular debris.
  • The role of specific signaling pathways in regulating microglial functions, particularly phagocytosis and response to injury, remains an active area of research.

Purpose of the Study:

  • To investigate the role of TAM receptor tyrosine kinases (Mer and Axl) in regulating microglial functions.
  • To determine the impact of TAM receptor signaling on apoptotic cell clearance and microglial response to central nervous system (CNS) injury.

Main Methods:

  • Utilized adult mice deficient in microglial Mer and Axl.
  • Employed live two-photon imaging to assess microglial process motility and response to injury.
  • Analyzed microglial phagocytosis of apoptotic cells during adult neurogenesis.
  • Examined microglial Axl expression in a mouse model of Parkinson's disease.

Main Results:

  • Mice lacking microglial Mer and Axl showed significant accumulation of apoptotic cells in neurogenic CNS regions.
  • Microglial phagocytosis of apoptotic cells during adult neurogenesis is regulated by TAM receptor ligands Gas6 and Protein S.
  • TAM-deficient microglia exhibited reduced process motility and delayed migration to sites of brain injury.
  • Microglial Axl expression was notably upregulated in a Parkinson's disease mouse model.

Conclusions:

  • TAM receptors (Mer and Axl) are critical regulators of microglial phagocytic clearance and response to CNS damage.
  • These findings identify TAM receptors as key controllers of microglial physiology.
  • TAM receptors represent potential therapeutic targets for CNS diseases characterized by impaired microglial function.

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