EHD4 is a novel regulator of urinary water homeostasis

Shamma S. Rahman, Alexandra E.J. Moffitt, Andrew J. Trease, Kirk W Foster, Matthew D. Storck, Hamid Band, Erika I Boesen

Research output: Contribution to journalArticle

Abstract

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 inner medullary 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 inner medullary principal cells appeared more dispersed, and the intensity of apical membrane staining for AQP2 was reduced significantly (by ∼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.

Original languageEnglish (US)
Pages (from-to)5217-5233
Number of pages17
JournalFASEB Journal
Volume31
Issue number12
DOIs
StatePublished - Jan 1 2017

Fingerprint

Aquaporin 2
Homeostasis
Knockout Mice
Water
Urine
Kidney
Osmolar Concentration
Proteins
Nephrons
Ducts
Recycling
Staining and Labeling
Membranes
Plasmas

Keywords

  • Aquaporin-2
  • Aquaporin-4
  • Arginine vasopressin
  • Endocytic recycling

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

EHD4 is a novel regulator of urinary water homeostasis. / Rahman, Shamma S.; Moffitt, Alexandra E.J.; Trease, Andrew J.; Foster, Kirk W; Storck, Matthew D.; Band, Hamid; Boesen, Erika I.

In: FASEB Journal, Vol. 31, No. 12, 01.01.2017, p. 5217-5233.

Research output: Contribution to journalArticle

Rahman, SS, Moffitt, AEJ, Trease, AJ, Foster, KW, Storck, MD, Band, H & Boesen, EI 2017, 'EHD4 is a novel regulator of urinary water homeostasis', FASEB Journal, vol. 31, no. 12, pp. 5217-5233. https://doi.org/10.1096/fj.201601182RR
Rahman SS, Moffitt AEJ, Trease AJ, Foster KW, Storck MD, Band H et al. EHD4 is a novel regulator of urinary water homeostasis. FASEB Journal. 2017 Jan 1;31(12):5217-5233. https://doi.org/10.1096/fj.201601182RR
Rahman, Shamma S. ; Moffitt, Alexandra E.J. ; Trease, Andrew J. ; Foster, Kirk W ; Storck, Matthew D. ; Band, Hamid ; Boesen, Erika I. / EHD4 is a novel regulator of urinary water homeostasis. In: FASEB Journal. 2017 ; Vol. 31, No. 12. pp. 5217-5233.
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