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Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways
Miriam Zacchia1, Xuefei Tian2, Enrica Zona3
1Division of Nephrology, Department of Cardio-Thoracic and Respiratory Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy; and miriamzacchia@virgilio.it.
Journal of the American Society of Nephrology : JASN
|April 22, 2018
Summary
Acid load stimulates renal citrate reabsorption via NaDC-1 by activating Pyk2/c-Src and Raf1-ERK1/2-p90RSK pathways, independent of endothelin signaling.
Area of Science:
- Nephrology
- Cellular signaling
- Molecular biology
Background:
- Urine citrate reabsorption occurs in the renal proximal tubule via the NaDC-1 cotransporter.
- Acid loads stimulate NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB) signaling.
Purpose of the Study:
- To investigate the specific signaling pathways mediating acid-induced NaDC-1 activity.
- To determine if Pyk2/c-Src and ERK1/2 pathways are involved in acid-induced NaDC-1 stimulation.
Main Methods:
- Using cultured kidney cells and Pyk2-null mice to study NaDC-1 activity.
- Employing [14C]-citrate uptake assays, immunoblotting, and protein inhibition studies.
- Investigating the role of Pyk2, c-Src, and the Raf1-ERK1/2-p90RSK pathway.
Main Results:
- Inhibition of Pyk2 or c-Src blocked acid-induced, but not ET-1-induced, NaDC-1 activity.
- Acid loading stimulated NaDC-1 activity in wild-type mice but not in Pyk2-null mice.
- The Raf1-ERK1/2-p90RSK pathway was essential for acid stimulation of NaDC-1.
Conclusions:
- Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling.
- These pathways are activated independently of the ET-1/ETB signaling pathway.
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