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Sugar transporter Slc37a2 regulates bonemetabolism in mice via a tubular lysosomalnetwork in osteoclasts

Sugar transporter Slc37a2 regulates bonemetabolism in mice via a tubular lysosomalnetwork in osteoclasts

Pei Ying Ng # 1Amy B P Ribet # 1Qiang Guo # 1 2Benjamin H Mullin 1 3Jamie W Y Tan 1Euphemie Landao-Bassonga 1Sébastien Stephens 4Kai Chen 1Jinbo Yuan 1Laila Abudulai 1 5 6Maike Bollen 5 6Edward T T T Nguyen 1Jasreen Kular 1John M Papadimitriou 7Kent Søe 8 9Rohan D Teasdale 10Jiake Xu 1Robert G Parton 11 12Hiroshi Takayanagi 13Nathan J Pavlos 14

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.

You can read more at: https://pubmed.ncbi.nlm.nih.gov/36810735/

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