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 language | English (US) |
|---|---|
| Article number | eaag3315 |
| Journal | Science Signaling |
| Volume | 11 |
| Issue number | 532 |
| DOIs | |
| State | Published - May 29 2018 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium. / Yu, Bo; Egbejimi, Anuoluwapo; Dharmat, Rachayata; Xu, Pei; Zhao, Zhenyang; Long, Bo; Miao, Hongyu; Chen, Rui; Wensel, Theodore G.; Cai, Jiyang; Chen, Yan.
In: Science Signaling, Vol. 11, No. 532, eaag3315, 29.05.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium
AU - Yu, Bo
AU - Egbejimi, Anuoluwapo
AU - Dharmat, Rachayata
AU - Xu, Pei
AU - Zhao, Zhenyang
AU - Long, Bo
AU - Miao, Hongyu
AU - Chen, Rui
AU - Wensel, Theodore G.
AU - Cai, Jiyang
AU - Chen, Yan
PY - 2018/5/29
Y1 - 2018/5/29
N2 - 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.
AB - 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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U2 - 10.1126/scisignal.aag3315
DO - 10.1126/scisignal.aag3315
M3 - Article
VL - 11
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 532
M1 - eaag3315
ER -