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Differential localisation and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise

Hodson, Nathan and McGlory, Chris and Oikawa, Sara Y. and Jeromson, Stewart and Song, Zhe and Ruegg, Markus A. and Hamilton, D. Lee and Phillips, Stuart M. and Philp, Andrew. (2017) Differential localisation and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise. American Journal of Physiology - Cell Physiology, 313 (6). C604-C611.

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Abstract

Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model. In basal samples, mTOR and the lysosomal marker LAMP2 were highly co-localized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery (WGA positive staining) (time effect; p=.025), with 39% (FED) and 26% (EXFED) increases in mTOR/WGA association observed 1h post-feeding/exercise. mTOR/WGA colocalisation continued to increase in EXFED at 3h (48% above baseline) whereas colocalisation decreased in FED (21% above baseline). A significant effect of condition (p=.05) was noted suggesting mTOR/WGA co-localization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3h post-exercise/feeding (p=.014). Rictor/WGA colocalization remained unaltered throughout the trial. Alterations in mTORC1 cellular location coincided with elevated S6K1 kinase activity, which rose to a greater extent in EXFED compared to FED at 1h post-exercise/feeding (p<.001), and only remained elevated in EXFED at the 3h time point (p=.037). Collectively these data suggest that mTORC1 redistribution within the cell is a fundamental response to resistance exercise and feeding, whereas mTORC2 is predominantly situated at the sarcolemma and does not alter localisation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
ISSN:0363-6143
e-ISSN:1522-1563
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:16 May 2018 06:14
Deposited On:16 May 2018 06:14

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