Mislocalization of K+ channels causes the renal salt wasting in EAST/SeSAME syndrome

Masayuki Tanemoto; Takaaki Abe; Shunya Uchida; Katsumasa Kawahara

doi:10.1016/j.febslet.2014.02.024

Mislocalization of K+ channels causes the renal salt wasting in EAST/SeSAME syndrome

FEBS Lett. 2014 Mar 18;588(6):899-905. doi: 10.1016/j.febslet.2014.02.024. Epub 2014 Feb 20.

Authors

Masayuki Tanemoto¹, Takaaki Abe², Shunya Uchida³, Katsumasa Kawahara⁴

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 174-8605, Japan. Electronic address: mtanemoto-tky@umin.ac.jp.
² Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8575, Japan.
³ Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 174-8605, Japan.
⁴ Department of Cellular and Molecular Physiology, Kitasato University Graduate School of Medical Sciences, Sagamihara 252-0374, Japan.

PMID: 24561201
DOI: 10.1016/j.febslet.2014.02.024

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.

Keywords: EAST/SeSAME syndrome; Epithelial sodium transport; Intracellular trafficking; Kidney; Potassium channel; Tubulopathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Cell Adhesion Molecules
Cell Adhesion Molecules, Neuronal / metabolism
Cell Polarity
Dogs
Guanylate Kinases
HEK293 Cells
Hearing Loss, Sensorineural / genetics
Hearing Loss, Sensorineural / metabolism*
Humans
Intellectual Disability / genetics
Intellectual Disability / metabolism*
Kcnj10 Channel
Kidney Tubules, Distal / metabolism*
Kir5.1 Channel
Madin Darby Canine Kidney Cells
Mutation, Missense
Potassium Channels, Inwardly Rectifying / genetics
Potassium Channels, Inwardly Rectifying / metabolism*
Protein Transport
Seizures / genetics
Seizures / metabolism*

Substances

Adaptor Proteins, Signal Transducing
Cell Adhesion Molecules
Cell Adhesion Molecules, Neuronal
Guanylate Kinases
Potassium Channels, Inwardly Rectifying
Kcnj10 Channel
KCNJ16 protein, human
Kir5.1 Channel
MAGI1 protein, human

Supplementary concepts

SeSAME syndrome