Genetic Dissection of TAM Receptor-Ligand Interaction in Retinal Pigment Epithelial Cell Phagocytosis

Tal Burstyn-Cohen*, Erin D. Lew, Paqui G. Través, Patrick G. Burrola, Joseph C. Hash, Greg Lemke

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


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.

Original languageAmerican English
Pages (from-to)1123-1132
Number of pages10
Issue number6
StatePublished - 20 Dec 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health (R01 AI077058 and R01 AI101400, to G.L.), the European Union (Marie Curie grant IRG-256319, to T. B.-C.), and the Israel Science Foundation (grant 984/12, to T. B.-C.), by the Salk Institute (NIH Cancer Center Grant CA014195), and by postdoctoral fellowships from the Leukemia and Lymphoma Society (to E.D.L.) and the Fundación Ramón Areces (to P.G.T.).


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