TAM receptor function in the retinal pigment epithelium
Abstract
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.
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Astrocyte engulfment ability is highly dependent on secreted factors; astrocyte-conditioned media, 5% serum or Protein S greatly increase synaptosome engulfment whereas fresh media does not.
“The engulfment ability of astrocytes was highly dependent on the presence of secreted factors, since addition of astrocyte-conditioned media (ACM), 5% serum or Protein S (a bridging molecule that bridges phosphatidylserine-MERTK interaction)9 greatly increased the amount of synaptosomes engulfed by astrocytes whereas addition of fresh media (unconditioned astrocyte growth media, AGM) did not (Fig.”
From Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways (2013) · cites this paper as [9]
Other TAM receptors such as TYRO3 and the lipid scavenger receptor CD36, both expressed in the RPE, may play a supporting role in OS phagocytosis.
“Aside from MERTK, there are data to suggest that other TAM receptors, such as TYRO3, and the lipid scavenger receptor CD36, both of which are expressed in the RPE (Ryeom et al., 1996; Prasad et al., 2006), may play a supporting role in OS phagocytosis.”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Prasad et al., 2006
Engagement of the αvβ5 integrin initiates a signaling cascade that triggers OS ingestion, predominantly mediated by MERTK, which is present in the RPE apical membrane.
“Engagement of the αvβ5 integrin initiates a signaling cascade that triggers OS ingestion, predominantly mediated by MERTK (Gal et al., 2000), a member of the Tyro-Axl-Mer (TAM) ingestion receptor family, that is present in the RPE apical membrane (Prasad et al., 2006).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Prasad et al., 2006
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References 54 · Cited by 270
- Authors
- Prasad, D., Rothlin, C. V., Burrola, P., Burstyn-Cohen, T., Lu, Q., Garcia de Frutos, P., & Lemke, G.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Lemke, Greg
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 33
- Issue
- 1
- Pages
- 96-108
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1996842103
- Cited by
- 270
- References
- 54
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 21 · 2023: 9 · 2022: 10 · 2021: 11 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 18 · 2016: 16 · 2015: 21 · 2014: 17 · 2013: 15 · 2012: 9
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Lupus Research Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- TAM receptors, MERTK, Tyro3, retinal pigment epithelium, Gas6, protein S, photoreceptor outer segment phagocytosis, photoreceptor degeneration, receptor tyrosine kinase signaling, ligand specificity
- MeSH terms
- c-Mer Tyrosine Kinase, Growth Arrest-Specific Protein 6, Animals, Cells, Cultured, Humans, Ligands, Pigment Epithelium of Eye, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Protein S, Mice, Knockout, Photoreceptor Cells, Vertebrate, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Mice
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