NDLI: Defective membrane expression of the Na+-HCO3 − cotransporter NBCe1 is associated with familial migraine

Content Provider	PubMed Central
Author	Suzuki, Masashi Paesschen, Wim Van Stalmans, Ingeborg Horita, Shoko Yamada, Hideomi Bergmans, Bruno A. Eric, Legius Florence, Riant Jonghe, Peter De Li, Yuehong Sekine, Takashi Igarashi, Takashi Fujimoto, Ichiro Mikoshiba, Katsuhiko Shimadzu, Mitsunobu Shiohara, Masaaki Braverman, Nancy Al-gazali, Lihadh Fujita, Toshiro Seki, George
Abstract	Homozygous mutations in SLC4A4, encoding the electrogenic Na+-HCO3 − 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 (Δ65bp) 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 Δ65bp 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.
Related Links	http://dx.doi.org/10.1073/pnas.1008705107
Ending Page	15968
Page Count	6
Starting Page	15963
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	36
Volume Number	107
Language	English
Publisher	National Academy of Sciences
Publisher Date	2010-09-07
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Physiological and pathophysiological roles of the electrogenic Na+-HCO3– cotransporter NBCe1

Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates the electrogenic Na/HCO3 cotransporter NBCe1-A expressed in Xenopus oocytes

Short-Term Regulation of Murine Colonic NBCe1-B (Electrogenic Na+/HCO3 − Cotransporter) Membrane Expression and Activity by Protein Kinase C

Identification of dominant negative effect of L522P mutation in the electrogenic Na+–HCO3 − cotransporter NBCe1

Secretagogue stimulation enhances NBCe1 (electrogenic Na+/HCO3 − cotransporter) surface expression in murine colonic crypts

Molecular mechanisms of renal and extrarenal manifestations caused by inactivation of the electrogenic Na+-HCO3 − cotransporter NBCe1

Electrogenic Na/HCO3 Cotransporter (NBCe1) Variants Expressed in Xenopus Oocytes: Functional Comparison and Roles of the Amino and Carboxy Termini

Relief of autoinhibition of the electrogenic Na-HCO3 cotransporter NBCe1-B: role of IRBIT vs. amino-terminal truncation

Effect of Human Carbonic Anhydrase II on the Activity of the Human Electrogenic Na/HCO3 Cotransporter NBCe1-A in Xenopus Oocytes

Defective membrane expression of the Na+-HCO3 − cotransporter NBCe1 is associated with familial migraine

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Defective membrane expression of the Na+-HCO3 − cotransporter NBCe1 is associated with familial migraine