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Proc Natl Acad Sci U S A
2010 Sep 07;10736:15963-8. doi: 10.1073/pnas.1008705107.
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Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine.
Suzuki M, Van Paesschen W, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, De Jonghe P, Li Y, Sekine T, Igarashi T, Fujimoto I, Mikoshiba K, Shimadzu M, Shiohara M, Braverman N, Al-Gazali L, Fujita T, Seki G.
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Homozygous mutations in SLC4A4, encoding the electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1, have been known to cause proximal renal tubular acidosis (pRTA) and ocular abnormalities. In this study, we report two sisters with pRTA, ocular abnormalities, and hemiplegic migraine. Genetic analysis ruled out pathological mutations in the known genes for familial hemiplegic migraine, but identified a homozygous 65-bp deletion (Delta65bp) in the C terminus of NBCe1, corresponding to the codon change S982NfsX4. Several heterozygous members of this family also presented glaucoma and migraine with or without aura. Despite the normal electrogenic activity in Xenopus oocytes, the Delta65bp mutant showed almost no transport activity due to a predominant cytosolic retention in mammalian cells. Furthermore, coexpression experiments uncovered a dominant negative effect of the mutant through hetero-oligomer formation with wild-type NBCe1. Among other pRTA pedigrees with different NBCe1 mutations, we identified four additional homozygous patients with migraine. The immunohistological and functional analyses of these mutants demonstrate that the near total loss of NBCe1 activity in astrocytes can cause migraine potentially through dysregulation of synaptic pH.
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000, Pubmed
Abuladze,
Structural organization of the human NBC1 gene: kNBC1 is transcribed from an alternative promoter in intron 3.
2000,
Pubmed Abuladze,
Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport.
2005,
Pubmed Alper,
Genetic diseases of acid-base transporters.
2002,
Pubmed Barnes,
Modulation of transmission gain by protons at the photoreceptor output synapse.
1993,
Pubmed Barrett,
Familial hemiplegic migraine.
2008,
Pubmed Bevensee,
An electrogenic Na(+)-HCO(-)(3) cotransporter (NBC) with a novel COOH-terminus, cloned from rat brain.
2000,
Pubmed
,
Xenbase Bok,
Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and kNBC1 in the rat eye.
2001,
Pubmed Borgula,
Light-evoked changes in extracellular pH in frog retina.
1989,
Pubmed Chesler,
Regulation and modulation of pH in the brain.
2003,
Pubmed Cursiefen,
Migraine and tension headache in high-pressure and normal-pressure glaucoma.
2000,
Pubmed De Fusco,
Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2.
2003,
Pubmed Demirci,
Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).
2006,
Pubmed
,
Xenbase Dichgans,
Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.
,
Pubmed Ducros,
The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel.
2001,
Pubmed Goadsby,
Recent advances in understanding migraine mechanisms, molecules and therapeutics.
2007,
Pubmed Headache Classification Subcommittee of the International Headache Society,
The International Classification of Headache Disorders: 2nd edition.
2004,
Pubmed Horita,
Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
2005,
Pubmed
,
Xenbase Igarashi,
Novel nonsense mutation in the Na+/HCO3- cotransporter gene (SLC4A4) in a patient with permanent isolated proximal renal tubular acidosis and bilateral glaucoma.
2001,
Pubmed Igarashi,
Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
1999,
Pubmed Inatomi,
Mutational and functional analysis of SLC4A4 in a patient with proximal renal tubular acidosis.
2004,
Pubmed
,
Xenbase Kao,
Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A.
2008,
Pubmed Li,
Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane.
2004,
Pubmed
,
Xenbase Lipton,
Migraine in the United States: epidemiology and patterns of health care use.
2002,
Pubmed Majumdar,
Localization of electrogenic Na/bicarbonate cotransporter NBCe1 variants in rat brain.
2008,
Pubmed Mirza,
Effect of topiramate on acid-base balance: extent, mechanism and effects.
2009,
Pubmed Newman,
Sodium-bicarbonate cotransport in retinal astrocytes and Müller cells of the rat.
1999,
Pubmed Ophoff,
Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.
1996,
Pubmed Pietrobon,
Neurobiology of migraine.
2003,
Pubmed Quilty,
Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis.
2002,
Pubmed Romero,
Electrogenic Na+/HCO3- cotransporters: cloning and physiology.
1999,
Pubmed Satoh,
Localization of Na+-HCO-3 cotransporter (NBC-1) variants in rat and human pancreas.
2003,
Pubmed Shirakabe,
IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1).
2006,
Pubmed
,
Xenbase Shrode,
Intracellular pH regulation in primary rat astrocytes and C6 glioma cells.
1994,
Pubmed Suzuki,
Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis.
2008,
Pubmed
,
Xenbase Thomsen,
The genetic spectrum of a population-based sample of familial hemiplegic migraine.
2007,
Pubmed Usui,
Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis.
2001,
Pubmed
