The DOI matches its Crossref record; 62 of the 63 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cites
Phagocytosis and clearance of apoptotic cells is mediated by MER
Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., & Matsushima, G. K. (2001) · Nature · doi:10.1038/35075603 · Cited by 1,215
The renewal of photoreceptor cell outer segments
Young, R. W. (1967) · The Journal of Cell Biology · doi:10.1083/jcb.33.1.61 · Cited by 1,184
Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat
D'Cruz, P. M. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.4.645 · Cited by 884
INHERITED RETINAL DYSTROPHY IN THE RAT
Dowling, J. E., & Sidman, R. L. (1962) · The Journal of Cell Biology · doi:10.1083/jcb.14.1.73 · Cited by 803
Stitt, T. N., Conn, G., Goret, M., Lai, C., Bruno, J., Radzlejewski, C., Mattsson, K., Fisher, J., Gies, D. R., Jones, P. F., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90520-0 · Cited by 733
Gal, A., Li, Y., Thompson, D. A., Weir, J., Orth, U., Jacobson, S. G., Apfelstedt-Sylla, E., & Vollrath, D. (2000) · Nature Genetics · doi:10.1038/81555 · Cited by 679
Manfioletti, G., Brancolini, C., Avanzi, G. C., & Schneider, C. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.8.4976 · Cited by 585
Nagata, K., Ohashi, K., Nakano, T., Arita, H., Zong, C., Hanafusa, H., & Mizuno, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30022 · Cited by 541
THE ROLE OF THE PIGMENT EPITHELIUM IN THE ETIOLOGY OF INHERITED RETINAL DYSTROPHY IN THE RAT
Bok, D., & Hall, M. O. (1971) · The Journal of Cell Biology · doi:10.1083/jcb.49.3.664 · Cited by 537
Self-citationMullen, R. J., & LaVail, M. M. (1976) · Science · doi:10.1126/science.1265483 · Cited by 529
Cited by
Sorted by citations
Items 101–145 of 145
Qin, J., Li, L., Zhang, D., Yu, H., Tan, H., Zhang, J., Deng, B., Kijlstra, A., & Yang, P. (2016) · Scientific Reports · doi:10.1038/srep26662 · Cited by 12
Cell culture conditions affect RPE phagocytic function
Karl, M., Valtink, M., Bednarz, J., & Engelmann, K. (2006) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-006-0451-y · Cited by 11
Li, Y., Zhao, R., & Dai, W. (2015) · Asian Journal of Andrology · doi:10.4103/1008-682x.172825 · Cited by 10
Efferocytosis in the Tumor Microenvironment
Vaught, D., Stanford, J. C., & Cook, R. S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-394447-4.30050-5 · Cited by 11
Opposite Roles of MerTK Ligands Gas6 and Protein S During Retinal Phagocytosis
Nandrot, E. F. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-75402-4_70 · Cited by 11
Diurnal Photoreceptor Outer Segment Renewal in Mice Is Independent of Galectin-3
Esposito, N. J., Mazzoni, F., Vargas, J. A., & Finnemann, S. C. (2021) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.62.2.7 · Cited by 9
Apoptosis and Clearance of the Secretory Mammary Epithelium
Jamie, C. B., & Rebecca, S. (2013) · InTech eBooks · doi:10.5772/52160 · Cited by 8
Losonczy, G., Vajas, A., Takács, L., Dzsudzsák, E., Fekete, Á., Márhoffer, É., Kardos, L., Ajzner, É., Hurtado, B., de Frutos, P. G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050181 · Cited by 8
MERTK retinopathy: biomarkers assessing vision loss
Sakti, D. H., Cornish, E. E., Mustafic, N., Zaheer, A., Retsas, S., Rajagopalan, S., Chung, C. W. T., Ewans, L., McCluskey, P., Nash, B. M., et al. (2021) · Ophthalmic Genetics · doi:10.1080/13816810.2021.1955278 · Cited by 7
Serum protein microarray analysis of patients with preeclampsia
Zhang, W. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.864 · Cited by 7
Synergistic Interaction of Tubby and Tubby-Like Protein 1 (Tulp1)
Caberoy, N. B. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_64 · Cited by 6
Müller, C., & Finnemann, S. C. (2020) · Springer eBooks · doi:10.1007/978-3-030-28384-1_3 · Cited by 7
Growth Arrest-Specific 6 (Gas6) and TAM Receptors in Mouse Platelets
Uras, F., Küçük, B., Özakpınar, Ö. B., & Demir, A. M. (2015) · Turkish Journal of Hematology · doi:10.4274/tjh.2013.0097 · Cited by 5
Molecules Involved in Recognition and Clearance of Apoptotic/Necrotic Cells and Cell Debris
Napirei, M., & Mannherz, H. G. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9293-0_4 · Cited by 5
Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema
Sugimoto, M., Kondo, M., Yasuma, T., D’Alessandro‐Gabazza, C. N., Toda, M., Imai, H., Nakamura, M., & Gabazza, E. C. (2021) · Scientific Reports · doi:10.1038/s41598-021-89870-5 · Cited by 4
Vitamin K and the Visual System—A Narrative Review
Mong, M. A. (2023) · Nutrients · doi:10.3390/nu15081948 · Cited by 5
On Your Marks… Get Bound… Internalize!
Law, A.-L., & Nandrot, E. F. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-0631-0_91 · Cited by 4
Carter, D. A., Nommiste, B., Coffey, P. J., & Carr, A. F. (2016) · Springer eBooks · doi:10.1007/978-3-319-30582-0_9 · Cited by 3
Autofluorescence from the Outer Retina and Subretinal Space
(2007) · Springer eBooks · doi:10.1007/978-3-540-71994-6_17 · Cited by 3
Efferocytosis in the Tumor Microenvironment
Vaught, D., Stanford, J. C., & Cook, R. S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.30050-5 · Cited by 4
Aziz, M., & Wang, P. (2014) · Springer eBooks · doi:10.1007/978-94-017-8765-9_10 · Cited by 2
TYRO3 , AXL , MERTK and Their Ligands in Brain Metastases From Colorectal Cancers
Noblanc, A., Dkhissi, F., Guichet, P., Lebeau, L., Milin, S., Emambux, S., Roussille, P., Evrard, C., Karayan, L., Tougeron, D., et al. (2026) · Cancer Medicine · doi:10.1002/cam4.71869 · Cited by 1
Dóra, S. J., Marika, T., Doró, Z., Nagymihály, R., Josifovska, N., Facskó, A., & Goran, P. (2014) · SZTE Publicatio Repozitórium (University of Szeged) · Cited by 1
Nandrot, E. F., & Finnemann, S. C. (2004) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789812561756_0014 · Cited by 1
Vitamin K and the Visual System: A Narrative ReviewPreprint
Mong, M. A. (2023) · Preprints.org · doi:10.20944/preprints202302.0049.v1 · Cited by 1
Caracterització del gen GAS6 i associació amb malalties humanes
Miralles, X. M. I. (2006) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
The Soluble Form of the Axl Receptor Tyrosine Kinase
Ekman, C. J. (2010) · Lund University Publications (Lund University)
A multifaceted study of the receptor tyrosine kinase Axl with focus on Renal Cell Carcinoma
Gustafsson, A. (2009) · Lund University Publications (Lund University)
THE ROLE OF THE TAM FAMILY OF RECEPTOR PTKS IN RETINAL HOMEOSTASIS
Prasad, D. (2006) · eScholarship (California Digital Library)
Phagocytosis of Retinal Rod and Cone Photoreceptors
Farnoodian, M., Kinter, J. B., Aghdam, S. Y., Zaitoun, I. S., Christine, M. S., Khoh‐Reiter, S., Sokolowski, S. A., Jessen, B. A., Evans, M. G., Dalvie, D., et al. (2015)
AN UPDATE ON PATHOGENESIS OF SYSTEMIC LUPUS ERYTHEMATOSUS (REVIEW)
Ahmadpoor, P., Dalili, N., & Rostami, M. (2014)
Shelby, S. J. (2012) · Deep Blue (University of Michigan)
Saraon, P. (2014) · TSpace (University of Toronto)
Verdan, F. F. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2016.tde-07012016-154146
A systemically-delivered stem cell therapy for dry age related macular degeneration
Pay, S. L. (2017) · IUScholarWorks (Indiana University) · doi:10.7912/c2006q
Soluble CD93 is an Apoptotic Cell Opsonin Recognized by the α x β 2 IntegrinPreprint
Blackburn, J. W. D., Lau, D. H. C., Ellins, J., Kipp, A., Pawlak, E. N., Dikeakos, J. D., & Heit, B. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/341933 · Cited by 1
Ativação de macrófagos M1/M2 pela eferocitose de células apoptóticas infectadas
Salina, A. C. G. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2020.tde-25082020-090635
Sipahioğlu, H., Özel, M., Onuk, S., Yetkin, M. F., Yücesoy, F. S., Akın, A. K., & Başkol, G. (2023) · Neurology Asia · doi:10.54029/2023chw
Müller, C., & Finnemann, S. C. (2024) · Springer eBooks · doi:10.1007/978-3-031-35055-9_3
The role of Axl/Mertk/Tyro3 receptor tyrosine kinases in the clearance of apoptotic cells
Seitz, H. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/acdt-6997
CD14 and TLR4 contribute to the circadian regulation of retinal phagocytosis as co-receptorsPreprint
Hajem, L. D., Enderlin, J., Rieu, Q., Krim, S., Parnasse, J. C., Materne, C., Marcelin, G., Huby, T., & Nandrot, E. F. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.26.708367
Circadian regulation of the retinal pigment epithelium–photoreceptor complex
Milićević, N. (2020) · theses.fr (ABES) · doi:10.70675/2a3b679cz473bz4c14zb33az700581cd794a
Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer
Benzakour, O., Kaissouni, Y., Pardo, O. E., & Dkhissi, F. (2026) · Biochemical Journal · doi:10.1042/bcj20260110 · Cited by 2
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
