Zhou Yuehan, Skelton Lara A, Xu Lumei, Chandler Margaret P, Berthiaume Jessica M, Boron Walter F
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio
J Am Soc Nephrol. 2016 Sep;27(9):2616-21. doi: 10.1681/ASN.2015040439. Epub 2016 Feb 2.
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.
血液pH值的调节对生命的几乎每个方面都至关重要，这要求肾近端小管（PT）根据血液中[CO2]和[HCO3(-)]的变化来调整其H(+)分泌速率（几乎与HCO3(-)重吸收速率JHCO3相同）。然而，CO2/HCO3(-)传感机制仍未得到充分表征。由于受体酪氨酸激酶抑制剂使PT中的JHCO3对CO2浓度变化不敏感，我们推测受体蛋白酪氨酸磷酸酶-γ（RPTPγ）与细胞外CO2或HCO3(-)结合的结构特征有助于监测血液中CO2/HCO3(-)浓度。我们现在报告，PT在面向血液的膜上表达RPTPγ。此外，小鼠中RPTPγ的缺失消除了JHCO3对CO2和HCO3(-)的敏感性以及全身酸中毒期间血液pH值的正常防御。因此，RPTPγ似乎是一种对pH稳态至关重要的新型细胞外CO2/HCO3(-)传感器。
