Genetic dissection of TAM receptor-ligand interaction in retinal pigment epithelial cell phagocytosis
Open accessAbstract
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.
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Deletion of either Gas6 or Protein S alone does not affect retinal function in mice, but mice lacking both develop moderate to severe retinal degeneration, demonstrating that at least one ligand is required for MERTK activation.
“While deletion of either ligand alone does not affect retinal function in mice (Hall et al., 2005; Burstyn-Cohen et al., 2012), mice lacking both Gas6 and Protein S do develop moderate to severe retinal degeneration, demonstrating that at least one ligand is required for MERTK activation (Burstyn-Cohen et al., 2012).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Burstyn-Cohen et al., 2012
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- Authors
- Burstyn-Cohen, T., Lew, E. D., Través, P. G., Burrola, P. G., Hash, J. C., & Lemke, G.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Lemke, Greg
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 76
- Issue
- 6
- Pages
- 1123-1132
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3530147
- OpenAlex
- W2045857922
- Cited by
- 163
- References
- 50
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 15 · 2023: 14 · 2022: 16 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 15 · 2017: 18 · 2016: 11 · 2015: 14 · 2014: 11 · 2013: 4
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Israel Science Foundation (984/12)
- Marie Curie (IRG-256319)
- National Institutes of Health (R01 AI077058, R01 AI101400, CA014195)
- European Commission
- Fundación Ramón Areces
- Leukemia and Lymphoma Society
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- TAM receptors, Mer receptor, Gas6, protein S, ligand-receptor interactions, retinal pigment epithelium, photoreceptor outer segment phagocytosis, photoreceptor cell death, receptor tyrosine kinase, retinal development
- MeSH terms
- c-Mer Tyrosine Kinase, Growth Arrest-Specific Protein 6, Animals, Disease Models, Animal, Epithelial Cells, Ligands, Phagocytosis, Proto-Oncogene Proteins, Retinitis Pigmentosa, Cell Death, Protein S, Mice, Knockout, Photoreceptor Cells, Vertebrate, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Mice, Retinal Pigment Epithelium, Retinal Photoreceptor Cell Outer Segment
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