Role of NH(2) and COOH termini in targeting, stability, and activity of sodium bicarbonate cotransporter 1

American Journal of Physiology. Renal Physiology
Doris Joy D EspirituJose A L Arruda

Abstract

Sodium bicarbonate cotransporter 1 (NBC1) mediates 80% of bicarbonate reabsorption by the kidney, but the molecular determinants for activity, targeting, and cell membrane stability are poorly understood. We generated truncation mutants involving the entire NH(2) (DeltaN424) or the entire COOH (DeltaC92) terminus and examined the effects of these truncations on targeting, cell membrane stability, and NBC1 activity. DeltaN424 and DeltaC92 targeted to the plasma membrane of HEK293 cells or to the basolateral membrane of opossum kidney (OK) cells at 24 h but did not display NBC1 activity. Unlike the NBC1 wild-type and the DeltaN424, DeltaC92 expression was significantly decreased in the basolateral membrane at 48 h and yet the total DeltaC92 expression in the cell was constant. We found that decreased DeltaC92 expression in the basolateral membrane was due to increased endocytosis and mistargeting to the apical membrane. Increased endocytosis was prevented when both DeltaN424 and DeltaC92 were cotransfected together and more stable expression of DeltaC92 was observed. Immunoprecipitation studies using NBC1 antibody specific for the COOH epitope were able to detect the COOH truncated NBC1 when probed with NH(2) epitope-specific ant...Continue Reading

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Citations

Apr 6, 2013·Pflügers Archiv : European journal of physiology·Osamu YamazakiGeorge Seki
Sep 17, 2009·Antioxidants & Redox Signaling·Simon NagelChristopher J Schofield
May 19, 2009·The Journal of Experimental Biology·Walter F BoronMark D Parker
Apr 17, 2013·Physiological Reviews·Mark D Parker, Walter F Boron
Nov 20, 2016·Biological Chemistry·Yung-Ning Chang, Eric R Geertsma
Feb 1, 2018·American Journal of Physiology. Cell Physiology·Mark D Parker
Oct 31, 2006·Seminars in Nephrology·Angelito A BernardoJose A L Arruda

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