SLC1A5 provides glutamine and asparagine necessary for bone development in mice
Deepika Sharma,
Yilin Yu,
Leyao Shen,
Guo-Fang Zhang,
Courtney M Karner
Affiliations
Deepika Sharma
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States
Yilin Yu
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Leyao Shen
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
Guo-Fang Zhang
Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, Durham, United States; Department of Medicine, Duke University School of Medicine, Durham, United States
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States; Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. University of Texas Southwestern Medical Center at Dallas, Dallas, United States
Osteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition and production. How osteoblasts obtain or maintain intracellular amino acid production is poorly understood. Here, we identify SLC1A5 as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we show SLC1A5 acts cell autonomously to regulate protein synthesis and osteoblast differentiation. SLC1A5 provides both glutamine and asparagine which are essential for osteoblast differentiation. Mechanistically, glutamine and to a lesser extent asparagine support amino acid biosynthesis. Thus, osteoblasts depend on Slc1a5 to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.
