4.7 Article

The role of L-type amino acid transporter 1 (Slc7a5) during in vitro myogenesis

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 323, Issue 2, Pages C595-C605

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00162.2021

Keywords

amino acids; leucine; myoblast; protein; satellite cells

Funding

  1. Office of the Vice -Chancellor for Research, University of Illinois
  2. Division of Nutritional Sciences Vision 20/20 Program, University of Illinois
  3. NSERC Discovery Grant [RGPIN-2017-40320]
  4. Chilean National Agency for Research and Development (ANID)
  5. Canadian Institutes of Health Canada Graduate Scholarship-Master 's
  6. Egg Nutrition Center Fellowship
  7. Doctoral Fellowship for Advancement of Biological Perspectives for Exercise Interventions Across the Lifespan

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This study investigates the role of L-type amino acid transporter 1 (LAT1) in muscle regeneration and myogenesis. The results suggest that LAT1 is expressed by myoblasts and is involved in normal myogenesis in vitro. The findings provide insight into the regulation of muscle remodeling by dietary factors.
Satellite cells are required for muscle regeneration, remodeling, and repair through their activation, proliferation, and differentiation; however, how dietary factors regulate this process remains poorly understood. The L-type amino acid transporter 1 (LAT1) transports amino acids, such as leucine, into mature myofibers, which then stimulate protein synthesis and anabolic signaling. However, whether LAT1 is expressed on myoblasts and is involved in regulating myogenesis is unknown. The aim of this study was to characterize the expressional and functional relevance of LAT1 during different stages of myogenesis and in response to growth and atrophic conditions in vitro. We determined that LAT1 is expressed by C2C12 and human primary myoblasts, and its gene expression is lower during differentiation (P < 0.05). Pharmacological inhibition and genetic knockdown of LAT1 impaired myoblast viability, differentiation, and fusion (all P < 0.05). LAT1 protein content in C2C12 myoblasts was not significantly altered in response to different leucine concentrations in cell culture media or in two in vitro atrophy models. However, LAT1 content was decreased in myotubes under atrophic conditions in vitro (P < 0.05). These findings indicate that LAT1 is stable throughout myogenesis and in response to several in vitro conditions that induce muscle remodeling. Further, amino acid transport through LAT1 is required for normal myogenesis in vitro.

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