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Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts

Author

Listed:
  • Pei Ying Ng

    (The University of Western Australia)

  • Amy B. P. Ribet

    (The University of Western Australia)

  • Qiang Guo

    (The University of Western Australia
    Central South University)

  • Benjamin H. Mullin

    (The University of Western Australia
    Sir Charles Gairdner Hospital)

  • Jamie W. Y. Tan

    (The University of Western Australia)

  • Euphemie Landao-Bassonga

    (The University of Western Australia)

  • Sébastien Stephens

    (Griffith University)

  • Kai Chen

    (The University of Western Australia)

  • Jinbo Yuan

    (The University of Western Australia)

  • Laila Abudulai

    (The University of Western Australia
    The University of Western Australia
    The University of Western Australia)

  • Maike Bollen

    (The University of Western Australia
    The University of Western Australia)

  • Edward T. T. T. Nguyen

    (The University of Western Australia)

  • Jasreen Kular

    (The University of Western Australia)

  • John M. Papadimitriou

    (PathWest Laboratory Medicine WA)

  • Kent Søe

    (University of Southern Denmark
    Odense University Hospital)

  • Rohan D. Teasdale

    (The University of Queensland)

  • Jiake Xu

    (The University of Western Australia)

  • Robert G. Parton

    (The University of Queensland
    The University of Queensland)

  • Hiroshi Takayanagi

    (The University of Tokyo)

  • Nathan J. Pavlos

    (The University of Western Australia)

Abstract

Osteoclasts are giant bone-digesting cells that harbor specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition and spatiotemporal organization of SLs remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 of the solute carrier 37 family (Slc37a2) as a SL sugar transporter. We demonstrate in mice that Slc37a2 localizes to the SL limiting membrane and that these organelles adopt a hitherto unnoticed but dynamic tubular network in living osteoclasts that is required for bone digestion. Accordingly, mice lacking Slc37a2 accrue high bone mass owing to uncoupled bone metabolism and disturbances in SL export of monosaccharide sugars, a prerequisite for SL delivery to the bone-lining osteoclast plasma membrane. Thus, Slc37a2 is a physiological component of the osteoclast’s unique secretory organelle and a potential therapeutic target for metabolic bone diseases.

Suggested Citation

  • Pei Ying Ng & Amy B. P. Ribet & Qiang Guo & Benjamin H. Mullin & Jamie W. Y. Tan & Euphemie Landao-Bassonga & Sébastien Stephens & Kai Chen & Jinbo Yuan & Laila Abudulai & Maike Bollen & Edward T. T. , 2023. "Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36484-2
    DOI: 10.1038/s41467-023-36484-2
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    References listed on IDEAS

    as
    1. Norihiro Nakamura & Jennie R. Lill & Qui Phung & Zhaoshi Jiang & Corey Bakalarski & Ann de Mazière & Judith Klumperman & Megan Schlatter & Lélia Delamarre & Ira Mellman, 2014. "Endosomes are specialized platforms for bacterial sensing and NOD2 signalling," Nature, Nature, vol. 509(7499), pages 240-244, May.
    2. Amy Chow & Derek Toomre & Wendy Garrett & Ira Mellman, 2002. "Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane," Nature, Nature, vol. 418(6901), pages 988-994, August.
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