title: Genetic dissection of TAM receptor-ligand interaction in retinal pigment epithelial cell phagocytosis.
abstract: Although TAM receptor tyrosine kinases play key roles in immune regulation, cancer metastasis, and viral infection, the relative importance of the two TAM ligands-Gas6 and Protein S-has yet to be resolved in any setting in vivo. We have now performed a genetic dissection of ligand function in the retina, where the TAM receptor Mer is required for the circadian phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells. This process is severely attenuated in Mer mutant mice, which leads to photoreceptor death. We find that retinal deletion of either Gas6 or Protein S alone yields retinae with a normal number of photoreceptors. However, concerted deletion of both ligands fully reproduces the photoreceptor death seen in Mer mutants. These results demonstrate that Protein S and Gas6 function as independent, bona fide Mer ligands, and are, to a first approximation, interchangeable with respect to Mer-driven phagocytosis in the retina.
authors.affiliation: The Institute of Dental Sciences, Hebrew University - Hadassah, Jerusalem 91120, Israel. talbu@ekmd.huji.ac.il
authors.forename: Tal
authors.initials: T
authors.lastname: Burstyn-Cohen
authors.forename: Erin D
authors.initials: ED
authors.lastname: Lew
authors.forename: Paqui G
authors.initials: PG
authors.lastname: Través
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Burrola
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Hash
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D017293:Protein S / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000503:physiopathology*; D000076202:c-Mer 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; D000099255:Growth Arrest-Specific Protein 6; C490767:Mertk protein, mouse