Protein‐carbohydrate ingestion alters Vps34 cellular localization independent of changes in kinase activity in human skeletal muscle
| Autor: | Stewart Jeromson, Jessica R. Dent, Zhe Song, Leigh Breen, Simon W. Jones, Andrew Philp, Nathan Hodson, James Murray, D. Lee Hamilton, Mary F. O’Leary, Thomas Nicholson |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Physiology Muscle Fibers Skeletal Carbohydrates P70-S6 Kinase 1 mTORC1 030204 cardiovascular system & hematology Cell Line Eating Mice Young Adult 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Humans Kinase activity Muscle Skeletal Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Cellular localization Nutrition and Dietetics biology Myogenesis Chemistry TOR Serine-Threonine Kinases fungi Skeletal muscle General Medicine Middle Aged Class III Phosphatidylinositol 3-Kinases Endocrinology medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Experimental Physiology. 105:2178-2189 |
| ISSN: | 1469-445X 0958-0670 |
| Popis: | New findings What is the central question of the study? Is Vps34 a nutrient-sensitive activator of mTORC1 in human skeletal muscle? What is the main finding and its importance? We show that altering nutrient availability, via protein-carbohydrate feeding, does not increase Vps34 kinase activity in human skeletal muscle. Instead, feeding increased Vps34-mTORC1 co-localization in parallel to increased mTORC1 activity. These findings may have important implications in the understanding nutrient-induced mTORC1 activation in skeletal muscle via interaction with Vps34. Abstract The Class III PI3Kinase, Vps34, has recently been proposed as a nutrient sensor, essential for activation of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1). We therefore investigated the effects of increasing nutrient availability through protein-carbohydrate (PRO-CHO) feeding on Vps34 kinase activity and cellular localization in human skeletal muscle. Eight young, healthy males (21 ± 0.5 yrs, 77.7 ± 9.9 kg, 25.9 ± 2.7 kg/m2 , mean ± SD) ingested a PRO-CHO beverage containing 20/44/1 g PRO/CHO/FAT respectively, with skeletal muscle biopsies obtained at baseline and 1 h and 3 h post-feeding. PRO-CHO feeding did not alter Vps34 kinase activity, but did stimulate Vps34 translocation toward the cell periphery (PRE (mean ± SD) - 0.273 ± 0.040, 1 h - 0.348 ± 0.061, Pearson's Coefficient (r)) where it co-localized with mTOR (PRE - 0.312 ± 0.040, 1 h - 0.348 ± 0.069, Pearson's Coefficient (r)). These alterations occurred in parallel to an increase in S6K1 kinase activity (941 ± 466% of PRE at 1 h post-feeding). Subsequent in vitro experiments in C2C12 and human primary myotubes displayed no effect of the Vps34-specific inhibitor SAR405 on mTORC1 signalling responses to elevated nutrient availability. Therefore, in summary, PRO-CHO ingestion does not increase Vps34 activity in human skeletal muscle, whilst pharmacological inhibition of Vps34 does not prevent nutrient stimulation of mTORC1 in vitro. However, PRO-CHO ingestion promotes Vps34 translocation to the cell periphery, enabling Vps34 to associate with mTOR. Therefore, our data suggests that interaction between Vps34 and mTOR, rather than changes in Vps34 activity per se may be involved in PRO-CHO activation of mTORC1 in human skeletal muscle. |
| Databáze: | OpenAIRE |
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