title: TAM receptors regulate multiple features of microglial physiology.
abstract: 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.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fourgeaud
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Paqui G
authors.initials: PG
authors.lastname: Través
authors.affiliation: Waitt Advanced Biophotonics Center, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tufail
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.|Neuroscience Masters Program, University of Strasbourg, Strasbourg, France.
authors.forename: Humberto
authors.initials: H
authors.lastname: Leal-Bailey
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Lew
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Burrola
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Perri
authors.initials: P
authors.lastname: Callaway
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Anna
authors.initials: A
authors.lastname: Zagórska
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT USA 06520.
authors.forename: Carla V
authors.initials: CV
authors.lastname: Rothlin
authors.affiliation: Waitt Advanced Biophotonics Center, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Axel
authors.initials: A
authors.lastname: Nimmerjahn
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.|Immunobiology and Microbial Pathogenesis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA USA 92037.
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D017628:Microglia / Q000502:physiology*; D055495:Neurogenesis; D010300:Parkinson Disease / Q000378:metabolism; D010587:Phagocytosis; D017293:Protein S / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche; D015854:Up-Regulation; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D017293:Protein S; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C490767:Mertk protein, mouse; C000722290:AXL receptor tyrosine kinase, mouse