title: ABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis.
abstract: Phagocytosis of shed photoreceptor outer segments (POSs) by retinal pigment epithelial (RPE) cells is critical to retinal homeostasis and shares many conserved signaling pathways with other phagocytes, including extrinsic regulations. Phagocytotic ligands are the key to cargo recognition, engulfment initiation, and activity regulation. In this study, we identified intracellular protein ATP-binding cassette subfamily F member 1 (ABCF1) as a novel RPE phagocytotic ligand by a new approach of functional screening. ABCF1 was independently verified to extrinsically promote phagocytosis of shed POSs by D407 RPE cells. This finding was further corroborated with primary RPE cells and RPE explants. Internalized POS vesicles were colocalized with a phagosome marker, suggesting that ABCF1-mediated engulfment is through a phagocytic pathway. ABCF1 was released from apoptotic cells and selectively bound to shed POS vesicles and apoptotic cells, possibly via externalized phosphatidylserine. ABCF1 is predominantly expressed in POSs and colocalized with the POS marker rhodopsin, providing geographical convenience for regulation of RPE phagocytosis. Collectively these results suggest that ABCF1 is released from and binds to shed POSs in an autocrine manner to facilitate RPE phagocytosis through a conserved pathway. Furthermore, the new approach is broadly applicable to many other phagocytes and will enable systematic elucidation of their ligands to understand extrinsic regulation and cargo recognition.
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136.
authors.forename: Feiye
authors.initials: F
authors.lastname: Guo
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Life Sciences, University of Nevada-Las Vegas, Las Vegas, NV 89154.
authors.forename: Nora
authors.initials: N
authors.lastname: Caberoy
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Alvarado
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, Miami, FL 33136 w.li@med.miami.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D008024:Ligands; D051379:Mice; D010587:Phagocytosis; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: C115776:ABCF1 protein, human; C000622631:ABCF1 protein, mouse; D018528:ATP-Binding Cassette Transporters; D008024:Ligands