A tyrosine-based signal regulates h/k-atpase mediated potassium
resorption in the kidney..
Wang, Tong, Nathalie Courtois-Coutry, Gerhard Giebisch, and Michael J.
Caplan.
Department of Cellular and Molecular Physiology, Yale University
School of Medicine, 333 Cedar Streetm New Haven, CT 06510
APStracts 5:0138F, 1998.
Isoforms of the H,K-ATPase participate in active K resorption in the
renal collecting tubule. The cytoplasmic tail of the b-subunit of the
gastric H,K-ATPase includes a 4 amino acid motif which is highly
homologous to tyrosine-based endocytosis signals. We have generated
transgenic mice expressing an H,K-ATPase b-subunit in which the
tyrosine residue in this sequence has been mutated to alanine. Mice
expressing the mutated protein manifest constitutive hypersecretion
of gastric acid, demonstrating that the b-subunit tyrosine-based
motif is required for the regulated endocytosis of the H,K pump and
hence the cessation of gastric acid output. To test the possibility
that the tyrosine-based sequence in the tail of the H,K-ATPase b
-subunit plays a role in regulating the function of renal H,K-ATPases,
we examined renal K clearance in normal and in transgenic mice. Blood
pressure, urine volume, GFR, plasma Na and Na excretion are similar
in control and transgenic mice. However, plasma K concentrations are
significantly higher in transgenic mice (4.76+0.13 in transgenic and
4.12+0.04 in control, n=9, P<0.05) and K excretion is lower in the
transgenic animals (26.2+3.62 in transgenic and FEK%=50.1+4.78 in
control, n=9, P<0.01). These data suggest that the tyrosine-based
signal in the cytoplasmic tail of the H,K-ATPase b-subunit functions
in the kidney as it does in the stomach to internalize H,K pump and
thus inactivate pump function. Its elimination may result in the
constitutive presence of the pump at the cell surface and lead to
excessive urinary K resorption.
Received 1 December 1997; accepted in final form 14 August 1998.
APS Manuscript Number F372-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998