ABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis.

TitleABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis.
Publication TypeJournal Article
Year of Publication2015
AuthorsGuo, F, Ding, Y, Caberoy, N, Alvarado, G, Wang, F, Chen, R, Li, W
JournalMol Biol Cell
Date Published2015 Jun 15

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.

Alternate JournalMol. Biol. Cell
PubMed ID25904329
PubMed Central IDPMC4462947
Grant ListP30-EY014801 / EY / NEI NIH HHS / United States
R01GM094449 / GM / NIGMS NIH HHS / United States
R21HD075372 / HD / NICHD NIH HHS / United States