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Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells
Abstract
Survival of the retina requires the daily phagocytosis of photoreceptor outer segments (OS) by the overlying retinal pigment epithelium (RPE). OS phagocytosis by cultured RPE requires serum and we have recently shown that the vitamin K-dependent serum protein, Gas6, can completely replace serum in this process. Surprisingly, however, we show here that 4-month-old Gas6 knockout mice have normal appearing retinas, except for a reduced ratio of outer segment to inner segment length. We also show that removal of Gas6 from serum does not abrogate the ability of serum to support OS phagocytosis by rat RPE. Both of these findings suggest the presence of an additional serum ligand that is able to support OS phagocytosis by RPE cells. Protein S (PS) is a vitamin K-dependent serum protein with a high degree of structural similarity to Gas6, and a well characterized role in blood coagulation. We report here that recombinant rat PS is able to stimulate OS phagocytosis, and similar to Gas6, it does so through a Mer-dependent mechanism. This is the first demonstration of a common role for Gas6 and PS in any biological process. The existence of redundant ligands for Mer-dependent OS phagocytosis underscores the critical role of this process in the maintenance of retinal function.
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“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 Hall et al., 2005
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Metadata
- Authors
- Hall, M. O., Obin, M. S., Heeb, M. J., Burgess, B. L., & Abrams, T. A.
- Affiliations
- Ronald Reagan UCLA Medical Center (US)
- Tufts University (US)
- Scripps Research Institute (US)
- Corresponding author
- Hall, Michael O.
- ORCID
- Burgess, Barry L.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 81
- Issue
- 5
- Pages
- 581-591
- ISSN
- 0014-4835 (ISSN-L)
- OpenAlex
- W2009789841
- Cited by
- 145
- References
- 63
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 16 · 2013: 5 · 2012: 11
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Karl Kirchgessner Foundation
- National Institutes of Health (1r01ey013956-01a1)
- National Heart, Lung, and Blood Institute (HL 70002, R01HL070002)
- National Eye Institute (EY11705, EY 13078, EY 013956, EY-00331, P30EY013078)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- photoreceptor outer segment phagocytosis, retinal pigment epithelium, protein S, Gas6, MERTK, photoreceptor degeneration
- MeSH terms
- c-Mer Tyrosine Kinase, Growth Arrest-Specific Protein 6, Animals, Cells, Cultured, Epithelial Cells, Fluorescent Antibody Technique, Phagocytosis, Pigment Epithelium of Eye, Proto-Oncogene Proteins, Rod Cell Outer Segment, Stimulation, Chemical, Blotting, Northern, Protein S, Mice, Knockout, Receptor Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Mice, Rats
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