Renal calcium reabsorption involves the epithelial calcium channel ECaC1 (TRPV5) which is tightly regulated by 1,25(OH)2D3. As shown recently, TRPV5 is activated by the serum and glucocorticoid inducible kinase SGK1, a kinase transcriptionally upregulated by 1,25(OH)2D3. This stimulatory effect is due to enhanced TRPV5 abundance in the plasma membrane and requires the presence of the scaffold protein NHERF2 (sodium hydrogen exchanger regulating factor 2). The present study aims to define the molecular requirements for the interaction of TRPV5 with SGK1 and NHERF2. Pull-down experiments and overlay assays revealed that the TRPV5 C-tail interacts in a Ca2+
-independent manner with NHERF2. Deletion of the second but not of the first PDZ domain in NHERF2 abrogates the stimulating effect of SGK1/NHERF2 on TRPV5 protein abundance in the plasma membrane as quantified by chemiluminescence and electrophysiology. Thus, the second PDZ domain in NHERF2 is required for stabilization at or TRPV5 targeting to the plasma membrane. The experiments demonstrate the significance of SGK1 and NHERF2 as TRPV5 modulators which are likely to participate in the regulation of calcium homeostasis by 1,25(OH)2D3.
Prof. Dr. Florian Lang
Physiologisches Institut der Universität Tübingen
Gmelinstr. 5, D-72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
Accepted: July 10, 2004
Published online: December 11, 2009
Number of Print Pages : 8
Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)
Vol. 15, No. 1-4, Year 2005 (Cover Date: 2005)
Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)
For additional information: http://www.karger.com/journals/cpb
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