Purchase this article with an account.
Shan Ma, Aditya Venkatesh, Claudio Punzo; Loss of mTORC1 & mTORC2 but nor mTORC1 or mTORC2 leads to reduction in cone function.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):378.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Photoreceptors are metabolically highly active requiring phosphoinositide 3-kinase (PI3K) activity for long-term survival. The mechanistic target of rapamycin (mTOR) is a key regulator of cell metabolism downstream of PI3K integrating nutrient availability and growth factor signals. mTOR is found in two distinct complexes (mTORC1 & mTORC2) that are characterized by their unique accessory proteins raptor and rictor respectively. This study analyses the effect on cones of loss of mTORC1, which regulates mainly cell metabolism in response to nutrient availability and growth factor signals, and mTORC2, which regulates pro-survival mechanisms in response to growth factors. Concomitant loss of both mTOR complexes is analyzed as well.
Mice carrying conditional knockout alleles for raptor and rictor were crossed to a cone-specific Cre recombinase line to ablate mTORC1 and/or mTORC2 in cones. Cone function and survival was followed by electroretinogram and histological analyses.
Concomitant loss of mTORC1 and mTORC2 affected cone function but not survival, while individual loss of mTORC1 or mTORC2 had no effect on cone function or survival. Interestingly, red/green opsin expression was reduced ventrally for a period of 3-4 months starting at 3 months of age for loss of mTORC1 and 4 months of age for loss of mTORC2.
PI3K mediated pro-survival pathways are independent of both mTOR complexes. Although mTOR is key in regulating cell metabolism and PRs are metabolically highly active, mTOR does not regulate cell metabolism and growth in cones, suggesting that the metabolic transcriptome that is regulated by mTORC1 in other cells is independent of mTOR in cones.
This PDF is available to Subscribers Only