Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium

Bo Yu, Anuoluwapo Egbejimi, Rachayata Dharmat, Pei Xu, Zhenyang Zhao, Bo Long, Hongyu Miao, Rui Chen, Theodore G. Wensel, Jiyang Cai, Yan Chen

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Article numbereaag3315
JournalScience Signaling
Volume11
Issue number532
DOIs
StatePublished - May 29 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yu, B., Egbejimi, A., Dharmat, R., Xu, P., Zhao, Z., Long, B., Miao, H., Chen, R., Wensel, T. G., Cai, J., & Chen, Y. (2018). Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium. Science Signaling, 11(532), [eaag3315]. https://doi.org/10.1126/scisignal.aag3315