TAM receptors regulate multiple features of microglial physiology

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.