Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE

Document Type

Article

Publication Date

10-14-2016

Publication Title

The Journal of biological chemistry

Abstract

Renal cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na+/K+/2Cl- co-transporter NKCC2. Trafficking of NKCC2 to the apical surface regulates NKCC2-mediated NaCl absorption and blood pressure. The molecular mechanisms by which NKCC2 reaches the apical surface and their role in renal function and maintenance of blood pressure are poorly characterized. Here we report that NKCC2 interacts with the vesicle fusion protein VAMP3, and they co-localize at the TAL apical surface. We observed that silencing VAMP3 in vivo blocks constitutive NKCC2 exocytic delivery, decreasing the amount of NKCC2 at the TAL apical surface. VAMP3 is not required for cAMP-stimulated NKCC2 exocytic delivery. Additionally, genetic deletion of VAMP3 in mice decreased total expression of NKCC2 in the TAL and lowered blood pressure. Consistent with these results, urinary excretion of water and electrolytes was higher in VAMP3 knock-out mice, which produced more diluted urine. We conclude that VAMP3 interacts with NKCC2 and mediates its constitutive exocytic delivery to the apical surface. Additionally, VAMP3 is required for normal NKCC2 expression, renal function, and blood pressure.

Comments

This research was originally published in the Journal of Biological Chemistry. Author(s). Title. J. Biol. Chem. Year; Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology or © the Author(s). Original version available at: https://doi.org/10.1074/jbc.M116.735167

Medical Subject Headings

Animals; Blood Pressure; Cyclic AMP; Exocytosis; Gene Expression Regulation; Kidney; Male; Mice; Protein Transport; Rats; Rats, Sprague-Dawley; Sodium Chloride; Solute Carrier Family 12, Member 1; Vesicle-Associated Membrane Protein 3

PubMed ID

27551042

Volume

291

Issue

42

First Page

22063

Last Page

22073

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