International Journal of Molecular Sciences Article Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2 Dalal Bakhos-Douaihy 1,2, Elie Seaayfan 1,2,† , Sylvie Demaretz 1,2,†, Martin Komhoff 3,‡ and Kamel Laghmani 1,2,*,‡ 1 Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, 75006 Paris, France;
[email protected] (D.B.-D.);
[email protected] (E.S.);
[email protected] (S.D.) 2 CNRS, ERL8228, 75006 Paris, France 3 University Children’s Hospital, Philipps-University, 35043 Marburg, Germany;
[email protected] * Correspondence:
[email protected]; Tel.: +33-1-44-27-50-68; Fax: +33-1-44-27-51-19 † These authors contributed equally to this work. ‡ These authors contributed equally to this work. Abstract: Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life- threatening kidney disease. We previously showed that export from the ER constitutes the limiting step in NKCC2 maturation and cell surface expression. Yet, the molecular mechanisms involved in this process remain obscure. Here, we report the identification of chaperone stress 70 protein (STCH) and the stress-inducible heat shock protein 70 (Hsp70), as two novel binding partners of the ER-resident form of NKCC2. STCH knock-down increased total NKCC2 expression whereas Hsp70 knock-down or its inhibition by YM-01 had the opposite effect. Accordingly, overexpressing of STCH and Hsp70 exerted opposite actions on total protein abundance of NKCC2 and its folding mutants.