Secretion of L-glutamate from osteoclasts through transcytosis

Riyo Morimoto, Shunsuke Uehara, Shouki Yatsushiro, Narinobu Juge, Zhaolin Hua, Shigenori Senoh, Noriko Echigo, Mitsuko Hayashi, Toshihide Mizoguchi, Tadashi Ninomiya, Nobuyuki Udagawa, Hiroshi Omote, Akitsugu Yamamoto, Robert H. Edwards, Yoshinori Moriyama

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64 Citations (Scopus)

Abstract

Osteoclasts are involved in the catabolism of the bone matrix and eliminate the resulting degradation products through transcytosis, but the molecular mechanism and regulation of transcytosis remain poorly understood. Upon differentiation, osteoclasts express vesicular glutamate transporter 1 (VGLUT1), which is essential for vesicular storage and subsequent exocytosis of glutamate in neurons. VGLUT1 is localized in transcytotic vesicles and accumulates L-glutamate. Osteoclasts secrete L-glutamate and the bone degradation products upon stimulation with KCl or ATP in a Ca2+-dependent manner. KCl- and ATP-dependent secretion of L-glutamate was absent in osteoclasts prepared from VGLUT1-/- knockout mice. Osteoclasts express mGluR8, a class III metabotropic glutamate receptor. Its stimulation by a specific agonist inhibits secretion of L-glutamate and bone degradation products, whereas its suppression by a specific antagonist stimulates bone resorption. Finally, it was found that VGLUT1-/- mice develop osteoporosis. Thus, in bone-resorbing osteoclasts, L-glutamate and bone degradation products are secreted through transcytosis and the released L-glutamate is involved in autoregulation of transcytosis. Glutamate signaling may play an important role in the bone homeostasis.

Original languageEnglish
Pages (from-to)4175-4186
Number of pages12
JournalEMBO Journal
Volume25
Issue number18
DOIs
Publication statusPublished - Sep 20 2006

Keywords

  • Bone resorption
  • Osteoclast
  • Osteoporosis
  • Transcytosis
  • Vesicular glutamate transporter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Morimoto, R., Uehara, S., Yatsushiro, S., Juge, N., Hua, Z., Senoh, S., Echigo, N., Hayashi, M., Mizoguchi, T., Ninomiya, T., Udagawa, N., Omote, H., Yamamoto, A., Edwards, R. H., & Moriyama, Y. (2006). Secretion of L-glutamate from osteoclasts through transcytosis. EMBO Journal, 25(18), 4175-4186. https://doi.org/10.1038/sj.emboj.7601317