Internalization of NKCC2 is impaired in thick ascending limb of Henle in moesin knockout mice
Moesin is expressed in several types of cells including epithelial and endothelial cells. Several groups reported that moesin plays important roles in the regulation of the cellular motility, and the process of internalization of membrane proteins. However, the physiological roles of moesin in the kidney still remain unclear. Herein, we examined the physiological function of moesin in the kidney using moesin knockout (Msn −/y ) mice. There was no obvious abnormality in the renal morphology of Msn −/y mice. However, we found that Msn −/y mice exhibited mild hyperchloremia, and reduced glomerular filtration rate compared to wild type (WT) mice. Absolute electrolytes excretions of NaCl in Msn −/y mice were not significantly changed compared to WT mice. In the renal medulla, moesin was detected in thick ascending limb of Henle (TALH) as previously reported. To determine the physiological function of moesin in TALH, we examined the expression and subcellular localization of NKCC2 in Msn −/y mice. Interestingly, apical surface expression level, but not total expression of NKCC2 was increased in Msn −/y mice. Subcellular fractionation of renal medulla lysate and internalization assay using tubular suspension showed that the process of NKCC2 endocytosis is impaired. Since the distribution of NKCC2 in lipid raft fractions was decreased in Msn −/y mice, moesin may regulate the NKCC2 distribution to microdomain. These results suggest that moesin regulates the internalization of NKCC2. Furthermore, euhydration by water loading caused hyponatremina in Msn −/y mice, suggesting that dysfunction of moesin is associated with the nephrogenic syndrome of inappropriate antidiuresis (NSIAD).
KeywordsCytoskeleton Endocytosis Mineral metabolism Renal physiology
Sodium-potassium-chloride co-transporter 2
Thick ascending limb of Henle
We thank Professor Sachiko Tsukita and Dr. Atsushi Tamura for Msn -/y mice.
This research was supported in part by a Grant-in-Aid for Scientific research (25860693) from the Ministry of Education, Culture, Sports, Science and Technology of Japan to RH, the Salt Science Research Foundation, no.1320 to RH, and MEXT-supported Program for the Strategic Research Foundation at Private Universities to SA and RH.
Compliance with ethical standards
Conflict of interest
All the authors declared no competing interests.
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