mTORC1 and mTORC2 expression in inner retinal neurons and glial cells

The retina is one of the most metabolically active tissues, yet the processes that control retinal metabolism remains poorly understood. The mTOR complex (mTORC) that drives protein and lipid biogenesis and autophagy has been studied extensively in regards to retinal development and responses to opt...

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Bibliographic Details
Published in:Experimental eye research 2020-08, Vol.197, p.108131-108131, Article 108131
Main Authors: Losiewicz, Mandy K., Elghazi, Lynda, Fingar, Diane C., Rajala, Raju V.S., Lentz, Stephen I., Fort, Patrice E., Abcouwer, Steven F., Gardner, Thomas W.
Format: Article
Language:English
Subjects:
Animals
Disease Models, Animal
Gene Expression Regulation
Humans
Immunoblotting
Male
Mechanistic Target of Rapamycin Complex 1 - biosynthesis
Mechanistic Target of Rapamycin Complex 1 - genetics
Mechanistic Target of Rapamycin Complex 2 - biosynthesis
Mechanistic Target of Rapamycin Complex 2 - genetics
Mice
Mice, Inbred C57BL
mTORC
Protein synthesis
Raptor
Rats
Rats, Sprague-Dawley
Retina
Retinal Diseases - genetics
Retinal Diseases - metabolism
Retinal Diseases - pathology
Retinal ganglion cells
Retinal Ganglion Cells - metabolism
Retinal Ganglion Cells - pathology
Rictor
RNA - genetics
RNA - metabolism
Signal Transduction
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Summary:The retina is one of the most metabolically active tissues, yet the processes that control retinal metabolism remains poorly understood. The mTOR complex (mTORC) that drives protein and lipid biogenesis and autophagy has been studied extensively in regards to retinal development and responses to optic nerve injury but the processes that regulate homeostasis in the adult retina have not been determined. We previously demonstrated that normal adult retina has high rates of protein synthesis compared to skeletal muscle, associated with high levels of mechanistic target of rapamycin (mTOR), a kinase that forms multi-subunit complexes that sense and integrate diverse environmental cues to control cell and tissue physiology. This study was undertaken to: 1) quantify expression of mTOR complex 1 (mTORC1)- and mTORC2-specific partner proteins in normal adult rat retina, brain and liver; and 2) to localize these components in normal human, rat, and mouse retinas. Immunoblotting and immunoprecipitation studies revealed greater expression of raptor (exclusive to mTORC1) and rictor (exclusive for mTORC2) in normal rat retina relative to liver or brain, as well as the activating mTORC components, pSIN1 and pPRAS40. By contrast, liver exhibits greater amounts of the mTORC inhibitor, DEPTOR. Immunolocalization studies for all three species showed that mTOR, raptor, and rictor, as well as most other known components of mTORC1 and mTORC2, were primarily localized in the inner retina with mTORC1 primarily in retinal ganglion cells (RGCs) and mTORC2 primarily in glial cells. In addition, phosphorylated ribosomal protein S6, a direct target of the mTORC1 substrate ribosomal protein S6 kinase beta-1 (S6K1), was readily detectable in RGCs, indicating active mTORC1 signaling, and was preserved in human donor eyes. Collectively, this study demonstrates that the inner retina expresses high levels of mTORC1 and mTORC2 and possesses active mTORC1 signaling that may provide cell- and tissue-specific regulation of homeostatic activity. These findings help to define the physiology of the inner retina, which is key for understanding the pathophysiology of optic neuropathies, glaucoma and diabetic retinopathy. •mTORC1 and mTORC2 and component proteins are highly expressed in normal adult rat retina compared to brain and liver.•mTORC1 and ribosomal protein S6 are localized primarily to retinal ganglion cells of human, rat and mouse retinas.•mTORC2 localizes primarily in retinal glial cell
ISSN:0014-4835
1096-0007
DOI:10.1016/j.exer.2020.108131