Kidney Week

Abstract: FR-PO612

Syntaxin 3 Is Essential for Renal Proximal Tubular Reabsorption

Session Information

• Genetic Diseases: Tubulopathies
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Okushima, Hiroki, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Hiroki Okushima,

• Inoue, Kazunori, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Kazunori Inoue,

• Imai, Atsuhiro, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Atsuhiro Imai,

• Katsuma, Yusuke, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Yusuke Katsuma,

• Matsumoto, Ayumi, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Ayumi Matsumoto,

• Matsui, Isao, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Isao Matsui,

• Isaka, Yoshitaka, Department of Nephrology Osaka University Graduate School of Medicin, Suita, Osaka, Japan

Yoshitaka Isaka,

Background

Transporters at the apical membrane of renal proximal tubular epithelial cells (PTEC) are essential for reabsorbing water and electrolytes from primary urine. However, how these transporters are trafficked to the apical membrane remains uncertain. Syntaxin 3 (STX3) is a molecule that belongs to the membrane fusion-associated protein superfamily. The study aims to investigate the role of STX3 in the trafficking of transporters to the apical membrane in PTEC.

Methods

Localization of STX3 in mouse and human kidneys were analyzed by immunohistochemistry. Mice with floxed Stx3 were crossed with tamoxifen (Tam)-inducible PTEC-specific Cre-expressing mice (Ndrg1-CreERT2 Stx3^fl/fl (Stx3 cKO)). Samples of the Stx3 cKO mice were analyzed 1, 2, and 6 months after tamoxifen injection. Urinary electrolytes, urinary glucose, and urinary low molecular weight proteins were quantified to determine the presence of a Fanconi syndrome-like phenotype. The expression levels and localization of various transporters of PTEC were examined by immunohistochemistry. The localization of transport vesicles and brush border in PTEC were analyzed by electron microscopy.

Results

STX3 was localized at the apical membrane of PTEC, both in humans and mice. Increased urinary excretion of phosphate, glucose, and low molecular weight proteins were found in Stx3 cKO mice compared to control (Ctrl) mice. Urinary calcium excretion and serum creatinine levels in Stx3 cKO mice were similar to those in Ctrl mice. Immunohistochemical analyses revealed that sodium phosphate transporter 2a was distributed intracellularly and sodium-glucose transporter 2 expression was reduced in the PTECs of Stx3 cKO mice. Apical brush border membranes were diffusely shortened, and intracellular vesicles were accumulated in the sub-apical areas of the PTECs in Stx3 cKO mice.

Conclusion

These results suggest that STX3 is critical for the apical trafficking of various transporters that regulate urinary reabsorption in PTEC.

Funding

• Private Foundation Support