TAM receptor function in the retinal pigment epithelium.
The TAM receptor tyrosine kinase Mer is expressed by cells of the retinal pigment epithelium (RPE), and genetic studies have demonstrated that Mer is essential for RPE function. RPE cells that lack Mer exhibit a severely compromised ability to phagocytose the distal ends of photoreceptor (PR) outer segments, which leads to the complete postnatal degeneration of photoreceptors and to blindness. Although in vitro experiments have implicated Gas6 as the critical TAM ligand for this process, we find that Gas6 mutant mice have a histologically intact retina with no photoreceptor degeneration. We further find that, in addition to Mer, RPE cells also express another TAM receptor--Tyro 3--and that both of these receptors are instead activated independently by the Gas6-related ligand Protein S. This protein is also expressed by RPE cells. Finally, we demonstrate that loss of Mer function is accompanied by a substantial down-regulation in Tyro 3 as well. These observations indicate that both Mer and Tyro 3 act in mouse RPE cells and suggest that their biologically relevant ligand in these cells is Protein S.
Prasad
Dipti
D
Molecular Neurobiology Laboratory, The Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Rothlin
Carla Vanina
CV
Burrola
Patrick
P
Burstyn-Cohen
Tal
T
Lu
Qingxian
Q
Garcia de Frutos
Pablo
P
Lemke
Greg
G
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000648:ultrastructure; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D017293:Protein S; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C490767:Mertk protein, mouse; C513478:Tyro3 protein, mouse