Phagocytosed photoreceptor outer segments activate mTORC1 in the retinal pigment epithelium

Science Signaling
Bo YuYan Chen

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.

References

Nov 25, 1997·Proceedings of the National Academy of Sciences of the United States of America·S C FinnemannE Rodriguez-Boulan
Mar 4, 2000·Human Molecular Genetics·P M D'CruzD Vollrath
Apr 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Bimal N DesaiStuart L Schreiber
Jan 31, 2003·Investigative Ophthalmology & Visual Science·Jacque L DuncanDouglas Vollrath
Jul 19, 2003·Genes & Development·Ken InokiKun-Liang Guan
Dec 15, 2004·The Journal of Experimental Medicine·Emeline F NandrotSilvia C Finnemann
Jul 1, 2005·Physiological Reviews·Olaf Strauss
Jul 19, 2006·The Journal of Biological Chemistry·Stefan M SchiekeToren Finkel
Apr 4, 2008·Investigative Ophthalmology & Visual Science·Yan ChenJiyang Cai
May 24, 2008·Science·Yasemin SancakDavid M Sabatini
Jul 8, 2008·Nature Cell Biology·Eunjung KimKun-Liang Guan
Sep 11, 2009·Investigative Ophthalmology & Visual Science·Nataliya V GordiyenkoIan M MacDonald
Feb 6, 2010·Physiology·Brian M Kevany, Krzysztof Palczewski
Jun 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Theodoros KantidakisRobert J White
Dec 8, 2010·The Journal of Clinical Investigation·Chen ZhaoDouglas Vollrath
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Dec 24, 2010·Nature·Shomit SenguptaDavid M Sabatini
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Libin ShangXiaodong Wang
Apr 9, 2011·Molecular Cell·Abdelhafid SaciChristopher L Carpenter
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer MartinezDouglas R Green
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Jun 14, 2012·Science Signaling·Agnes Roczniak-FergusonShawn M Ferguson
Jul 23, 2013·Cell·Ji-Young KimThomas A Ferguson
Oct 4, 2013·Molecular Biology of the Cell·Matej KrajcovicMichael Overholtzer
Oct 30, 2013·Nature Neuroscience·Mauro Costa-Mattioli, Lisa M Monteggia
Jan 5, 2014·The Journal of Cell Biology·Charles Betz, Michael N Hall
Feb 18, 2014·Cell·Constantinos DemetriadesAurelio A Teleman
Aug 13, 2014·The Journal of Biological Chemistry·Yusuke TakahashiJian-Xing Ma

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Citations

Jul 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Young-Mi GoYan Chen
Jan 11, 2019·International Journal of Molecular Sciences·Janusz BlasiakKai Kaarniranta
Dec 5, 2018·Oxidative Medicine and Cellular Longevity·Yi HuangJiyang Cai
Oct 2, 2019·International Journal of Molecular Sciences·Oyuna S KozhevnikovaNataliya G Kolosova
Dec 9, 2020·Development, Growth & Differentiation·Noriaki SasaiAgnes Ong Lee Chen
Dec 8, 2020·Frontiers in Immunology·Whijin Kwon, Spencer A Freeman
Feb 28, 2020·Progress in Retinal and Eye Research·Aparna LakkarajuDavid S Williams
May 17, 2021·The FEBS Journal·Daniela IntartagliaIvan Conte

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