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Circadian regulation of outer segments phagocytosis by RPE cells: more complexity than meets the eye
Author(s) -
Nandrot E.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.02171
Subject(s) - mertk , phagocytosis , internalization , microbiology and biotechnology , receptor , biology , retinal pigment epithelium , intracellular , retina , signal transduction , receptor tyrosine kinase , neuroscience , biochemistry
Summary Daily clearance of aged photoreceptor outer segments ( POS ) extremities is one of the main functions of retinal pigment epithelial ( RPE ) cells. Absence or deregulation of this process leads to early‐onset or age‐related retinal pathologies. Despite the permanent tight contact between POS and RPE microvilli, phagocytosis occurs only once a day. Over the years, the main molecules implicated in POS tethering and subsequent internalization have been identified. POS tips expose phosphatidylserines on the outer membrane portion to be cleared. Timely recognition of POS tips and phagocytosis synchronization are mediated by the MFG ‐E8–alphavbeta5 integrin ligand–receptor couple. This triggers intracellular signaling pathways leading to the activation of the Mer TK internalization receptor. While this draws a sequential scheme of events, things are far from being that simple. Recently new roles for Mer TK and implication of new receptors have been suggested. In contrast to macrophages that share a similar phagocytic machinery, the continuous contact between both cell types requires the strict regulation of phagocytosis launch and stop to ensure lifelong retinal function. Thus, at this point the puzzle is about to get much more complicated.