New molecular motif contributes to NKCC2 trafficking

Abstract

One of the most important functions of the kidney is the formation of urine and the maintenance of electrolyte and water homeostasis. The Na+–K+–2Cl− cotransporter (NKCC2) is a major contributor to this process by actively reabsorbing Na+, K+ and Cl− in the kidney’s loop of Henle. The properties of this transporter are the subject of a recent article in The Journal of Physiology by Marcoux et al. (2019) in which they report that variants of this protein alter trafficking of NKCC2, which ultimately influences the reabsorption of sodium chloride (NaCl) along the thick ascending limb of the loop of Henle (TAL). The TAL is one segment of the nephron and is of particular interest since approximately 25% of the Na+ in the glomerular filtrate is reabsorbed from it back into the circulation (Castrop & Schnermann, 2008; Ares et al. 2011; Marcoux et al. 2019). The magnitude of the reabsorption implies that this segment (and NKCC2) is important in the control of blood pressure and total body sodium homeostasis. In humans, NKCC2 is the major determinant of ion movement from the lumen of the TAL, across the tubular epithelium and back into the blood. NKCC2 is a membrane protein that has 12 transmembrane (TM) domains and a large intracellular loop near the middle of the molecule, a structure that is similar to other related membrane ion transporters