Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3.

Autor: Zhou Y; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio., Skelton LA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio., Xu L; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio., Chandler MP; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio., Berthiaume JM; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio., Boron WF; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio walter.boron@case.edu.
Jazyk: angličtina
Zdroj: Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2016 Sep; Vol. 27 (9), pp. 2616-21. Date of Electronic Publication: 2016 Feb 02.
DOI: 10.1681/ASN.2015040439
Abstrakt: Regulation of blood pH-critical for virtually every facet of life-requires that the renal proximal tubule (PT) adjust its rate of H(+) secretion (nearly the same as the rate of HCO3 (-) reabsorption, JHCO3 ) in response to changes in blood [CO2] and [HCO3 (-)]. Yet CO2/HCO3 (-) sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-γ (RPTPγ) that are consistent with binding of extracellular CO2 or HCO3 (-) facilitate monitoring of blood CO2/HCO3 (-) concentrations. We now report that PTs express RPTPγ on blood-facing membranes. Moreover, RPTPγ deletion in mice eliminated the CO2 and HCO3 (-) sensitivities of JHCO3 as well as the normal defense of blood pH during whole-body acidosis. Thus, RPTPγ appears to be a novel extracellular CO2/HCO3 (-) sensor critical for pH homeostasis.
(Copyright © 2016 by the American Society of Nephrology.)
Databáze: MEDLINE