2010 Fiscal Year Final Research Report
Functional NBCe1 regulation by proteins'interaction
| Project/Area Number |
20590971
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMADA Hideomi The University of Tokyo, 医学部附属病院, 助教 (60396752)
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| Co-Investigator(Kenkyū-buntansha) |
GEORGE Seki 東京大学, 医学部附属病院, 講師 (30206619)
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| Project Period (FY) |
2008 – 2010
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| Keywords | NBC1(NBCe1) / RTA |
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| Research Abstract |
NBC1(NBCe1) belongs to bicarbonate transporter family(SLC4). This transporter plays an important role of adjusting the intracellular and/or extracellular pH to maintain the concentration of bicarbonate. The dysfunction of NBC1 brings on several and severe symptoms enough to threaten the life. This disease causes not only severe proximal renal tubular acidosis, but also symptoms of severe ocular-abnormalities (band-keratopathy, cataract, and glaucoma). Some patients suffering from these abnormalities develop blindness. They also have a high rate of migraine occurrence. Because NBC1 presents in the glia cells of the brain, NBC1 must work and maintain pH of the synaptic cleft. As NBC1 controls activities of neurotransmitters by pH in the cleft, the NBC1 mutants, which dose not express in the membrane, can not control right stable pH of the synaptic cleft. Because low pH of the cleft induces the abnormal signal of neurotransmitters, patients must have such a migraine. In addition, we reported that among several NBC1 SNPs, K558R had less activity of NBC1. NBC1 works on the membrane as a dimeric form. We also showed some of NBC1 mutants exert dominant negative effects on the wild-type NBC1. This fact raises a possibility that SNPs of NBC1 may cause migraine. The investigation of NBC1 may help further clarify the pathogenesis of migraine.
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[Journal Article] Severe Metabolic Acidosis Causes Early Lethality in NBC1 W516X Knock-in Mice as a Model of Human Isolated Proximal Renal Tubular Acidosis.2011
Author(s)
Lo Y, BS, Yang S, Seki G, Yamada H, Horita S, Yamazaki O, Fujita T, MD, Usui T, Tsai J, Yu I, PhD6, Lin S, Lin S
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Journal Title
Kidney Int 9
Pages: 730-741
Peer Reviewed
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[Journal Article] Defective membrane expression of the Na^+-HCO_3^- cotransporter NBCe1 is associated with familial migraine.2010
Author(s)
Suzuki M, Paesschen WV, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, Jonghe PD, Li Y, Sekine T, Igarashi T, Fujimoto I, Mikoshiba M, Shimadzu M, Shiohara M, Braverman N, Al-Gazali L, Fujita Y, Seki G
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Journal Title
Proc Natl Acad Sci U S A 107
Pages: 15963-15968
Peer Reviewed
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[Journal Article] Human sodium-phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.2010
Author(s)
Jutabha P, Anzai N, Kitamura K, Taniguchi A, Kaneko S, Yan K, Yamada H, Shimada H, Kimura T, Katada T, Fukutomi T, Tomita K, Urano W, Yamanaka H, Seki G, Fujita T, Moriyama Y, Yamada A, Uchida S, Michael F.Wempe MF, Endou H, Sakurai H
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Journal Title
J Biol Chem 285
Pages: 35123-32
Peer Reviewed
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[Journal Article] Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis.2008
Author(s)
Suzuki M, Vaisbich M, Yamada H, Horita S, Li Y, Sekine T, Moriyama N, Igarashi T, Endo Y, Cardoso T, de Sa L, Koch H, Seki G, Fujita, T
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Journal Title
Pflugers Arch 455
Pages: 583-593
Peer Reviewed
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