title: Secretion of L-glutamate from osteoclasts through transcytosis.
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.
authors.affiliation: Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Riyo
authors.initials: R
authors.lastname: Morimoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Uehara
authors.forename: Shouki
authors.initials: S
authors.lastname: Yatsushiro
authors.forename: Narinobu
authors.initials: N
authors.lastname: Juge
authors.forename: Zhaolin
authors.initials: Z
authors.lastname: Hua
authors.forename: Shigenori
authors.initials: S
authors.lastname: Senoh
authors.forename: Noriko
authors.initials: N
authors.lastname: Echigo
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Omote
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Moriyama
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D008954:Models, Biological; D010010:Osteoclasts / Q000378:metabolism* / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D050598:Vesicular Glutamate Transport Protein 1 / Q000172:deficiency / Q000235:genetics
chemical_list: D018094:Receptors, Metabotropic Glutamate; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C111435:metabotropic glutamate receptor 8; D018698:Glutamic Acid