title: Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Skelton
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Lumei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Chandler
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Berthiaume
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio walter.boron@case.edu.
authors.forename: Walter F
authors.initials: WF
authors.lastname: Boron
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D051379:Mice; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000502:physiology*
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: bicarbonate transport; kidney; metabolic acidosis; pH; proximal tubule; receptor protein tyrosine phosphatase
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