EHD4 is a novel regulator of urinary water homeostasis

Article

关键词: KIDNEY COLLECTING DUCT;    SHORT-TERM STIMULATION;    THICK ASCENDING LIMB;    AQP2 TRAFFICKING;    SUBCELLULAR-LOCALIZATION;    AQUAPORIN-2 TRAFFICKING;    DIFFERENTIAL REGULATION;    MEMBRANE TRANSLOCATION;    CL-COTRANSPORTER;    PLASMA-MEMBRANE;   

DOI  :  10.1096/fj.201601182RR

来源: SCIE

【 摘 要 】

The Eps15-homology domain-containing (EHD) protein family comprises 4 members that regulate endocytic recycling. Although the kidney expresses all 4 EHD proteins, their physiologic roles are largely unknown. This study focused on EHD4, which we found to be expressed differentially across nephron segments with the highest expression in the innermedullary collecting duct. Under baseline conditions, Ehd42/2 [EHD4-knockout (KO)] mice on a C57Bl/6 background excreted a higher volume of more dilute urine than control C57Bl/6 wild-type (WT) mice while maintaining a similar plasma osmolality. Urine excretion after an acute intraperitoneal water load was significantly increased in EHD4-KO mice compared to WT mice, and although EHD4-KO mice concentrated their urine during 24-h water restriction, urinary osmolality remained significantly lower than in WT mice, suggesting that EHD4 plays a role in renal water handling. Total aquaporin 2 (AQP2) and phospho-S256-AQP2 (pAQP2) protein expression in the inner medulla was similar in the two groups in baseline conditions. However, localization of both AQP2 and pAQP2 in the renal innermedullary principal cells appeared more dispersed, and the intensity of apical membrane staining for AQP2 was reduced significantly (by similar to 20%) in EHD4-KO mice compared to WT mice in baseline conditions, suggesting an important role of EHD4 in trafficking of AQP2. Together, these data indicate that EHD4 play important roles in the regulation of water homeostasis.-Rahman, S. S., Moffitt, A. E. J., Trease, A. J., Foster, K. W., Storck, M. D., Band, H., Boesen, E. I. EHD4 is a novel regulator of urinary water homeostasis.

【 授权许可】

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