Research ArticleCell Biology

Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium

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Sci. Signal.  29 May 2018:
Vol. 11, Issue 532, eaag3315
DOI: 10.1126/scisignal.aag3315

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Activating mTORC1 with phagocytosis

Every morning, photoreceptor outer segments in the retina are shed, phagocytosed by the retinal pigment epithelium, and degraded to enable renewal. Defects in this process contribute to retinal degeneration. Using retinal pigment epithelial cell lines and retinal tissues from mice, Yu et al. found that internalized photoreceptor outer segments served as a platform for the assembly and activation of mTORC1, a multiprotein complex that regulates metabolic pathways. The authors suggest that this mTORC1 activation process may switch metabolic pathways in the retinal pigment epithelium when degradation of photoreceptor outer segments is initiated.

Abstract

The retinal pigment epithelium (RPE) transports nutrients and metabolites between the microvascular bed that maintains the outer retina and photoreceptor neurons. The RPE removes photoreceptor outer segments (POS) by receptor-mediated phagocytosis, a process that peaks in the morning. Uptake and degradation of POS initiates signaling cascades in the RPE. Upstream stimuli from various metabolic activities converge on mechanistic target of rapamycin complex 1 (mTORC1), and aberrant mTORC1 signaling is implicated in aging and age-related degeneration of the RPE. We measured mTORC1-mediated responses to RPE phagocytosis in vivo and in vitro. During the morning burst of POS shedding, there was transient activation of mTORC1-mediated signaling in the RPE. POS activated mTORC1 through lysosome-independent mechanisms, and engulfed POS served as a docking platform for mTORC1 assembly. The identification of POS as endogenous stimuli of mTORC1 in the RPE provides a mechanistic link underlying the photoreceptor-RPE interaction in the outer retina.

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