title: Mislocalization of K+ channels causes the renal salt wasting in EAST/SeSAME syndrome.
abstract: The Kir4.1/Kir5.1 channel mediates basolateral K(+) recycling in renal distal tubules; this process is critical for Na(+) reabsorption at the tubules. Mutations in Kir4.1 are associated with EAST/SeSAME syndrome, a genetic disorder characterized by renal salt wasting. In this study, we found that MAGI-1 anchors Kir4.1 channels (Kir4.1 homomer and Kir4.1/Kir5.1 heteromer) and contributes to basolateral K(+) recycling. The Kir4.1 A167V mutation associated with EAST/SeSAME syndrome caused mistrafficking of the mutant channels and inhibited their expression on the basolateral surface of tubular cells. These findings suggest mislocalization of the Kir4.1 channels contributes to renal salt wasting.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 174-8605, Japan. Electronic address: mtanemoto-tky@umin.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tanemoto
authors.affiliation: Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8575, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 174-8605, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Cellular and Molecular Physiology, Kitasato University Graduate School of Medical Sciences, Sagamihara 252-0374, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016764:Cell Polarity; D004285:Dogs; D051528:Guanylate Kinases; D057809:HEK293 Cells; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D020125:Mutation, Missense; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012640:Seizures / Q000235:genetics / Q000378:metabolism*; D000098854:Kcnj10 Channel; D000097062:Kir5.1 Channel
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D051528:Guanylate Kinases; D024661:Potassium Channels, Inwardly Rectifying; D000098854:Kcnj10 Channel; C576242:KCNJ16 protein, human; D000097062:Kir5.1 Channel; C113338:MAGI1 protein, human
keywords: EAST/SeSAME syndrome; Epithelial sodium transport; Intracellular trafficking; Kidney; Potassium channel; Tubulopathy