ATP is a major chemical transmitter in purinergic signal transmission. Before secretion, ATP is stored in secretory vesicles found in purinergic cells. Although the presence of active transport mechanisms for ATP has been postulated for a long time, the proteins responsible for its vesicular accumulation remains unknown. The transporter encoded by the human and mouse SLC17A9 gene, a novel member of an anion transporter family, was predominantly expressed in the brain and adrenal gland. The mouse and bovine counterparts were associated with adrenal chromaffin granules. Proteoliposomes containing purified transporter actively took up ATP, ADP, and GTP by using membrane potential as the driving force. The uptake properties of the reconstituted transporter were similar to that of the ATP uptake by synaptic vesicles and chromaffin granules. Suppression of endogenous SLC17A9 expression in PC12 cells decreased exocytosis of ATP. These findings strongly suggest that SLC17A9 protein is a vesicular nucleotide transporter and should lead to the elucidation of the molecular mechanism of ATP secretion in purinergic signal transmission.
en-copyright= kn-copyright= en-aut-name=SawadaKeisuke en-aut-sei=Sawada en-aut-mei=Keisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=EchigoNoriko en-aut-sei=Echigo en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyajiTakaaki en-aut-sei=Miyaji en-aut-mei=Takaaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OtsukaMasato en-aut-sei=Otsuka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoAkitsugu en-aut-sei=Yamamoto en-aut-mei=Akitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University affil-num=7 en-affil= kn-affil=Nagahama Institute of Technology affil-num=8 en-affil= kn-affil=Okayama University en-keyword=chromaffin granule kn-keyword=chromaffin granule en-keyword=synaptic vesicle kn-keyword=synaptic vesicle en-keyword=ATP kn-keyword=ATP en-keyword=storage and exocytosis kn-keyword=storage and exocytosis en-keyword=purinergic signaling. kn-keyword=purinergic signaling. END start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=18 article-no= start-page=4175 end-page=4186 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=20060920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Secretion of L-glutamate from osteoclasts through transcytosis en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=MorimotoRiyo en-aut-sei=Morimoto en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeharaShunsuke en-aut-sei=Uehara en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YatsushiroShouki en-aut-sei=Yatsushiro en-aut-mei=Shouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HuaZhaolin en-aut-sei=Hua en-aut-mei=Zhaolin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenohShigenori en-aut-sei=Senoh en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EchigoNoriko en-aut-sei=Echigo en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiMitsuko en-aut-sei=Hayashi en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MizoguchiToshihide en-aut-sei=Mizoguchi en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NinomiyaTadashi en-aut-sei=Ninomiya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UdagawaNobuyuki en-aut-sei=Udagawa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoAkitsugu en-aut-sei=Yamamoto en-aut-mei=Akitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EdwardsRobert H en-aut-sei=Edwards en-aut-mei=Robert H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Departments of Neurology and Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine affil-num=6 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Institute for Oral Science, Matsumoto Dental University affil-num=10 en-affil= kn-affil=Institute for Oral Science, Matsumoto Dental University affil-num=11 en-affil= kn-affil=Department of Biochemistry, Matsumoto Dental University affil-num=12 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Cell Biology, Nagahama Institute of Bioscience and Technology affil-num=14 en-affil= kn-affil=Departments of Neurology and Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine affil-num=15 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences en-keyword=osteoclast kn-keyword=osteoclast en-keyword=vesicular glutamate transporter kn-keyword=vesicular glutamate transporter en-keyword=transcytosis kn-keyword=transcytosis en-keyword=bone resorption kn-keyword=bone resorption END start-ver=1.4 cd-journal=joma no-vol=102 cd-vols= no-issue=50 article-no= start-page=17923 end-page=17928 dt-received= dt-revised= dt-accepted= dt-pub-year=2007 dt-pub=20070925 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A human transporter protein that mediates the final excretion step for toxic organic cations en-subtitle= kn-subtitle= en-abstract= kn-abstract=In mammals, toxic electrolytes of endogenous and exogenous origin are excreted through the urine and bile. Before excretion, these compounds cross numerous cellular membranes in a transporter-mediated manner. However, the protein transporters involved in the final excretion step are poorly understood. Here, we show that MATE1, a human and mouse orthologue of the multidrug and toxin extrusion (MATE) family conferring multidrug resistance on bacteria, is primarily expressed in the kidney and liver, where it is localized to the luminal membranes of the urinary tubules and bile canaliculi. When expressed in HEK293 cells, MATE1 mediates H+-coupled electroneutral exchange of tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP). Its substrate specificity is similar to those of renal and hepatic H+-coupled organic cations (OCs) export. Thus, MATE1 appears to be the long searched for polyspecific OC exporter that directly transports toxic OCs into urine and bile.
en-copyright= kn-copyright= en-aut-name=OtsukaMasato en-aut-sei=Otsuka en-aut-mei=Masato kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoTakuya en-aut-sei=Matsumoto en-aut-mei=Takuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MorimotoRiyo en-aut-sei=Morimoto en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AriokaShigeo en-aut-sei=Arioka en-aut-mei=Shigeo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama University affil-num=2 en-affil= kn-affil=Okayama University affil-num=3 en-affil= kn-affil=Okayama University affil-num=4 en-affil= kn-affil=Okayama University affil-num=5 en-affil= kn-affil=Okayama University affil-num=6 en-affil= kn-affil=Okayama University en-keyword=MATE kn-keyword=MATE en-keyword=multidrug export kn-keyword=multidrug export en-keyword=excretion kn-keyword=excretion en-keyword=toxin kn-keyword=toxin en-keyword=urinary tubule kn-keyword=urinary tubule en-keyword=bile canaliculus kn-keyword=bile canaliculus en-keyword=organic cation kn-keyword=organic cation en-keyword=H+/cation antiport. kn-keyword=H+/cation antiport. END start-ver=1.4 cd-journal=joma no-vol=203 cd-vols= no-issue=1 article-no= start-page=107 end-page=116 dt-received= dt-revised= dt-accepted= dt-pub-year=2000 dt-pub=200001 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Luminal acidification of diverse organelles by V-ATPase in animal cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=Eukaryotic cells contain organelles bounded by a single membrane in the cytoplasm. These organelles have differentiated to carry out various functions in the pathways of endocytosis and exocytosis. Their lumina are acidic, with pH ranging from 4.5 to 6.5. This article describes recent studies on these animal cell organelles focusing on (1) the primary proton pump (vacuolar-type H+-ATPase) and (2) the functions of the organelle luminal acidity. We also discuss similarities and differences between vacuolar-type H+-ATPase and F-type ATPase. Our own studies and interests are emphasized. en-copyright= kn-copyright= en-aut-name=FutaiMasamitsu en-aut-sei=Futai en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OkaToshihiko en-aut-sei=Oka en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Sun-WadaGe-hong en-aut-sei=Sun-Wada en-aut-mei=Ge-hong kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanazawaHiroshi en-aut-sei=Kanazawa en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WadaYoh en-aut-sei=Wada en-aut-mei=Yoh kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University affil-num=2 en-affil= kn-affil=Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University affil-num=3 en-affil= kn-affil=Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University affil-num=4 en-affil= kn-affil=Department of Biology, Graduate School of Science, Osaka University affil-num=5 en-affil= kn-affil=Faculty of Pharmaceutical Sciences, Okayama University affil-num=6 en-affil= kn-affil=Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University en-keyword=ATPase kn-keyword=ATPase en-keyword=V-ATPase kn-keyword=V-ATPase en-keyword=organelle kn-keyword=organelle en-keyword=endomembrane kn-keyword=endomembrane en-keyword=proton pump kn-keyword=proton pump en-keyword=vacuolar-type ATPase. kn-keyword=vacuolar-type ATPase. END start-ver=1.4 cd-journal=joma no-vol=203 cd-vols= no-issue=1 article-no= start-page=117 end-page=125 dt-received= dt-revised= dt-accepted= dt-pub-year=2001 dt-pub=200101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Synaptic-like microvesicles, synaptic vesicle counterparts in endocrine cells, are involved in a novel regulatory mechanism for the synthesis and secretion of hormones en-subtitle= kn-subtitle= en-abstract= kn-abstract=Microvesicles in endocrine cells are the morphological and functional equivalent of neuronal synaptic vesicles. Microvesicles accumulate various neurotransmitters through a transmitter-specific vesicular transporter energized by vacuolar H+-ATPase. We found that mammalian pinealocytes, endocrine cells that synthesize and secrete melatonin, accumulate L-glutamate in their microvesicles and secrete it through exocytosis. Pinealocytes use L-glutamate as either a paracrine- or autocrine-like chemical transmitter in a receptor-mediated manner, resulting in inhibition of melatonin synthesis. In this article, we briefly describe the overall features of the microvesicle-mediated signal-transduction mechanism in the pineal gland and discuss the important role of acidic organelles in a novel regulatory mechanism for hormonal synthesis and secretion. en-copyright= kn-copyright= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HayashiMitsuko en-aut-sei=Hayashi en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamadaHiroshi en-aut-sei=Yamada en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YatsushiroShouki en-aut-sei=Yatsushiro en-aut-mei=Shouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IshioShougo en-aut-sei=Ishio en-aut-mei=Shougo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamamotoAkitsugu en-aut-sei=Yamamoto en-aut-mei=Akitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University affil-num=2 en-affil= kn-affil=Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University affil-num=3 en-affil= kn-affil=Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University affil-num=4 en-affil= kn-affil=Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University affil-num=5 en-affil= kn-affil=Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University affil-num=6 en-affil= kn-affil=Department of Physiology, Kansai Medical University en-keyword=V-ATPase kn-keyword=V-ATPase en-keyword=melatonin kn-keyword=melatonin en-keyword=L-glutamate kn-keyword=L-glutamate en-keyword=serotonin kn-keyword=serotonin en-keyword=paracrine kn-keyword=paracrine en-keyword=autocrine kn-keyword=autocrine en-keyword=pinealocyte kn-keyword=pinealocyte en-keyword=endocrine cell. kn-keyword=endocrine cell. END