Research ArticleBone Biology

The L-type amino acid transporter LAT1 inhibits osteoclastogenesis and maintains bone homeostasis through the mTORC1 pathway

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Science Signaling  09 Jul 2019:
Vol. 12, Issue 589, eaaw3921
DOI: 10.1126/scisignal.aaw3921

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LAT1 maintains bone density

Amino acids stimulate signaling through the mammalian target of rapamycin complex 1 (mTORC1). Both amino acids and mTORC1 signaling are important for bone homeostasis. Ozaki et al. found that the expression of Slc7a5, which encodes the amino acid transporter LAT1, was reduced in osteoclast precursors in a mouse model of postmenopausal osteoporosis. Mice lacking LAT1 in osteoclasts exhibited a reduction in bone mass due to the excessive differentiation and activity of these cells. In vitro experiments using osteoclasts derived from mutant mice demonstrated that LAT1-dependent signaling through mTORC1 repressed both the transcription and nuclear accumulation of the transcription factor and master regulator of osteoclast function NFATc1 through the NF-κB and Akt signaling pathways, respectively. These findings identify a molecular mechanism through which amino acids influence bone homeostasis.