Chapter Seven - Structure-function relationships in the renal NaCl cotransporter (NCC)

• Main Authors: Moreno, Erika, Heros, Paola de los, Plata, Consuelo, Cutler, Christopher P., Vega-Mateos, Antonio, Vázquez, Norma, Gamba, Gerardo
• Format: Text
• Language: unknown
• Published: Digital Commons@Georgia Southern 2019
• Subjects: NaCl cotransporter; sNCC; Thiazides; Gitelman syndrome; Arterial hypertension; Structure-function; WNKs; Biochemistry; Biophysics; and Structural Biology; Biology; spiny dogfish; Squalus acanthias
• Online Access: https://digitalcommons.georgiasouthern.edu/biology-facpubs/245; https://doi.org/10.1016/bs.ctm.2019.01.003

The thiazide-sensitive Na+-Cl− cotransporter (NCC) is the major pathway for salt reabsorption in the distal convoluted tubule, serves as a receptor for thiazide-type diuretics, and is involved in inherited diseases associated with abnormal blood pressure. The functional and structural characterization of NCC from different species has led us to gain insights into the structure-function relationships of the cotransporter. Here we present an overview of different studies that had described these properties. Additionally, we report the cloning and characterization of the NCC from the spiny dogfish (Squalus acanthias) kidney (sNCC). The purpose of the present study was to determine the main functional, pharmacological and regulatory properties of sNCC to make a direct comparison with other NCC orthologous. The sNCC cRNA encodes a 1033 amino acid membrane protein, when expressed in Xenopus oocytes, functions as a thiazide-sensitive Na–Cl cotransporter with NCC regulation and thiazide-inhibition properties similar to mammals, rather than to teleosts. However, the Km values for ion transport kinetics are significantly higher than those observed in the mammal species. In summary, we present a review on NCC structure-function relationships with the addition of the sNCC information in order to enrich the NCC cotransporter knowledge.