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

Ng, Pei Ying; Ribet, Amy B P; Guo, Qiang; Mullin, Benjamin H.; Tan, Jamie; Landao-Bassonga, Euphemie; Stephens, Sebastien Robert; Chen, Kai; Yuan, Jinbo; Abudulai, Laila N.; Bollen, Maike; Nguyen, Edward T T T; Kular, Jasreen; Papadimitriou, John; Søe, Kent; Teasdale, Rohan D.; Xu, Jiake; Parton, Robert G.; Takayanagi, Hiroshi; Pavlos, Nathan J.

doi:10.1038/s41467-023-36484-2

Cited by 9 publications

(4 citation statements)

References 73 publications

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“…Moreover, the chloride channels CLCN3 and CLCN7 are known to participate in bone resorption because CLCN7 ablation leads to osteopetrosis in humans ( Kornak et al, 2001 ) and CLCN3 contributes to organelle acidification in mice ( Okamoto et al, 2008 ). In addition, the membrane proteins LAMP1 and LAMP2 are expressed in lysosomes and autophagosomes, and they were localized to secretory vesicles associated to bone resorption along with CLCN3/CLCN7, at least in mice ( Ng et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions

Roy,

Mbous Nguimbus,

Badiane

et al. 2024

Life Sci. Alliance

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In overactive human osteoclasts, we previously identified an alternative splicing event inLGALS8, encoding galectin-8, resulting in decreased expression of the long isoform. Galectin-8, which modulates cell–matrix interactions and functions intracellularly as a danger recognition receptor, has never been associated with osteoclast biology. In human osteoclasts, inhibition of galectin-8 expression revealed its roles in bone resorption, osteoclast nuclearity, and mTORC1 signaling regulation. Galectin-8 isoform-specific inhibition asserted a predominant role for the short isoform in bone resorption. Moreover, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) proteomic analysis of galectin-8 isoforms performed in HEK293T cells identified 22 proteins shared by both isoforms. Meanwhile, nine interacting partners were specific for the short isoform, and none were unique to the long isoform. Interactors specific for the galectin-8 short isoform included cell adhesion proteins and lysosomal proteins. We confirmed the interactions of galectin-8 with CLCN3, CLCN7, LAMP1, and LAMP2, all known to localize to secretory vesicles, in human osteoclasts. Altogether, our study reveals direct roles of galectin-8 in osteoclast activity, mostly attributable to the short isoform.

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Section: Resultsmentioning

confidence: 99%

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions

Roy,

Mbous Nguimbus,

Badiane

et al. 2024

Life Sci. Alliance

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“…SLC37A2 deficiency and failure of phagosome resolution are also associated with impaired microglial cell migration and abnormalities in brain architecture 87 . SLC37A2 interestingly has also been linked to endolysosomal tubulation in osteoclasts and is required for appropriate remodeling of long bones 237 . To our knowledge, SLC37A2 mutations and polymorphisms have not yet been linked to disease processes but roles of phagosomal sugar transport in tissue remodeling are worthy of further study.…”

Section: Clinical Implications Of Impaired Resolutionmentioning

confidence: 99%

The resolution of phagosomes

Mylvaganam

Freeman

2023

Immunological Reviews

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SummaryPhagocytosis is a fundamental immunobiological process responsible for the removal of harmful particulates. While the number of phagocytic events achieved by a single phagocyte can be remarkable, exceeding hundreds per day, the same phagocytic cells are relatively long‐lived. It should therefore be obvious that phagocytic meals must be resolved in order to maintain the responsiveness of the phagocyte and to avoid storage defects. In this article, we discuss the mechanisms involved in the resolution process, including solute transport pathways and membrane traffic. We describe how products liberated in phagolysosomes support phagocyte metabolism and the immune response. We also speculate on mechanisms involved in the redistribution of phagosomal metabolites back to circulation. Finally, we highlight the pathologies owed to impaired phagosome resolution, which range from storage disorders to neurodegenerative diseases.

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“…Lysosomal dysfunction leads to various defects in lysosomal properties including pH imbalance, membrane potential disruption, enzymatic activity impairment, and abnormal autophagy. These lysosomal-mediat-ed diseases encompass a broad range of conditions, from LSDs to neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, hearing loss, obesity, osteopetrosis, fatty liver, cancers (lung, breast, prostate, and colon), and viral diseases (Ebola and SARS) [107][108][109][110][111][112][113][114][115][116][117][118].…”

Section: Lsds Linked To Ion Channelsmentioning

confidence: 99%

Unveiling the impact of lysosomal ion channels: balancing ion signaling and disease pathogenesis

Jung

Kim

Shin

et al. 2023

Korean J Physiol Pharmacol

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Ion homeostasis, which is regulated by ion channels, is crucial for intracellular signaling. These channels are involved in diverse signaling pathways, including cell proliferation, migration, and intracellular calcium dynamics. Consequently, ion channel dysfunction can lead to various diseases. In addition, these channels are present in the plasma membrane and intracellular organelles. However, our understanding of the function of intracellular organellar ion channels is limited. Recent advancements in electrophysiological techniques have enabled us to record ion channels within intracellular organelles and thus learn more about their functions. Autophagy is a vital process of intracellular protein degradation that facilitates the breakdown of aged, unnecessary, and harmful proteins into their amino acid residues. Lysosomes, which were previously considered protein-degrading garbage boxes, are now recognized as crucial intracellular sensors that play significant roles in normal signaling and disease pathogenesis. Lysosomes participate in various processes, including digestion, recycling, exocytosis, calcium signaling, nutrient sensing, and wound repair, highlighting the importance of ion channels in these signaling pathways. This review focuses on different lysosomal ion channels, including those associated with diseases, and provides insights into their cellular functions. By summarizing the existing knowledge and literature, this review emphasizes the need for further research in this field. Ultimately, this study aims to provide novel perspectives on the regulation of lysosomal ion channels and the significance of ion-associated signaling in intracellular functions to develop innovative therapeutic targets for rare and lysosomal storage diseases.

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

Cited by 9 publications

References 73 publications

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions

The resolution of phagosomes

Unveiling the impact of lysosomal ion channels: balancing ion signaling and disease pathogenesis

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