PMID- 28971834 OWN - NLM STAT- MEDLINE DCOM- 20171211 LR - 20220408 IS - 1522-1563 (Electronic) IS - 0363-6143 (Print) IS - 0363-6143 (Linking) VI - 313 IP - 6 DP - 2017 Dec 1 TI - Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise. PG - C604-C611 LID - 10.1152/ajpcell.00176.2017 [doi] AB - Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 [mTORC1-regulatory associated protein of mTOR (Raptor) positive] regulates skeletal muscle growth, whereas mTORC2 [rapamycin-insensitive companion of mTOR (Rictor) positive] regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilized immunohistochemical analysis to study the localization of mTOR complexes before and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in a unilateral exercise model. In basal samples, mTOR and the lysosomal marker lysosomal associated membrane protein 2 (LAMP2) were highly colocalized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery [wheat germ agglutinin (WGA)-positive staining] (time effect; P = 0.025), with 39% (FED) and 26% (EXFED) increases in mTOR/WGA association observed 1 h post-feeding/exercise. mTOR/WGA colocalization continued to increase in EXFED at 3 h (48% above baseline) whereas colocalization decreased in FED (21% above baseline). A significant effect of condition (P = 0.05) was noted suggesting mTOR/WGA colocalization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3 h post-exercise/feeding (P = 0.014). 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 with FED at 1 h post-exercise/feeding (P < 0.001), and only remained elevated in EXFED at the 3 h time point (P = 0.037). 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 localization. CI - Copyright (c) 2017 the American Physiological Society. FAU - Hodson, Nathan AU - Hodson N AD - School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom. FAU - McGlory, Chris AU - McGlory C AD - Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. FAU - Oikawa, Sara Y AU - Oikawa SY AD - Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. FAU - Jeromson, Stewart AU - Jeromson S AD - Faculty of Health Sciences and Sport, University of Stirling, Stirling, United Kingdom; and. FAU - Song, Zhe AU - Song Z AD - School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom. FAU - Ruegg, Markus A AU - Ruegg MA AD - Biozentrum, University of Basel, Basel, Switzerland. FAU - Hamilton, D Lee AU - Hamilton DL AD - Faculty of Health Sciences and Sport, University of Stirling, Stirling, United Kingdom; and. FAU - Phillips, Stuart M AU - Phillips SM AD - Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. FAU - Philp, Andrew AU - Philp A AUID- ORCID: 0000-0003-3860-4136 AD - School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom; a.philp@bham.ac.uk. LA - eng PT - Journal Article DEP - 20170927 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Dietary Carbohydrates) RN - 0 (Dietary Proteins) RN - 0 (LAMP2 protein, human) RN - 0 (Lysosomal-Associated Membrane Protein 2) RN - 0 (RICTOR protein, human) RN - 0 (RPTOR protein, human) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (Regulatory-Associated Protein of mTOR) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1) SB - IM MH - Adult MH - Dietary Carbohydrates/administration & dosage MH - Dietary Proteins/administration & dosage MH - *Eating MH - *Energy Metabolism MH - *Exercise MH - Humans MH - Lysosomal-Associated Membrane Protein 2/metabolism MH - Lysosomes/enzymology MH - Male MH - Mechanistic Target of Rapamycin Complex 1/*metabolism MH - Mechanistic Target of Rapamycin Complex 2/*metabolism MH - Muscle Contraction MH - Protein Transport MH - Proto-Oncogene Proteins c-akt/metabolism MH - Quadriceps Muscle/*enzymology MH - Rapamycin-Insensitive Companion of mTOR Protein/metabolism MH - Regulatory-Associated Protein of mTOR/metabolism MH - Resistance Training MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Sarcolemma/enzymology MH - Time Factors MH - Young Adult PMC - PMC5814591 OTO - NOTNLM OT - Raptor OT - Rictor OT - lysosome OT - mTORC1 OT - mTORC2 EDAT- 2017/10/04 06:00 MHDA- 2017/12/12 06:00 PMCR- 2018/12/01 CRDT- 2017/10/04 06:00 PHST- 2017/08/04 00:00 [received] PHST- 2017/09/22 00:00 [revised] PHST- 2017/09/23 00:00 [accepted] PHST- 2017/10/04 06:00 [pubmed] PHST- 2017/12/12 06:00 [medline] PHST- 2017/10/04 06:00 [entrez] PHST- 2018/12/01 00:00 [pmc-release] AID - ajpcell.00176.2017 [pii] AID - C-00176-2017 [pii] AID - 10.1152/ajpcell.00176.2017 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2017 Dec 1;313(6):C604-C611. doi: 10.1152/ajpcell.00176.2017. Epub 2017 Sep 27.