SLC1A5 provides glutamine and asparagine necessary for bone development in mice

  1. Deepika Sharma
  2. Yilin Yu
  3. Leyao Shen
  4. Guo-Fang Zhang
  5. Courtney M Karner  Is a corresponding author
  1. Duke University School of Medicine, United States
  2. University of Texas Southwestern Medical Center, United States
  3. Duke University Medical Center, United States

Abstract

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.

Data availability

All data generated or analyzed during this study are included in the manuscript.

Article and author information

Author details

  1. Deepika Sharma

    Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yilin Yu

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Leyao Shen

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Guo-Fang Zhang

    Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Courtney M Karner

    University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    courtney.karner@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0387-4486

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR076325)

  • Courtney M Karner

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR071967)

  • Courtney M Karner

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ernestina Schipani, University of Pennsylvania, United States

Ethics

Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal procedures were approved (APN 2020-102999) by the Animal Studies Committees at Duke University and the University of Texas Southwestern Medical Center at Dallas.

Version history

  1. Received: June 24, 2021
  2. Accepted: October 12, 2021
  3. Accepted Manuscript published: October 14, 2021 (version 1)
  4. Version of Record published: October 28, 2021 (version 2)

Copyright

© 2021, Sharma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Deepika Sharma
  2. Yilin Yu
  3. Leyao Shen
  4. Guo-Fang Zhang
  5. Courtney M Karner
(2021)
SLC1A5 provides glutamine and asparagine necessary for bone development in mice
eLife 10:e71595.
https://doi.org/10.7554/eLife.71595

Share this article

https://doi.org/10.7554/eLife.71595

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