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Na‐Cl cotransporter NCC inhibits Ca channel TRPV5 by hindering its trafficking to the plasma membrane
Author(s) -
Zhang Wei,
Na Tao,
Wu Guojin,
Jiang Yi,
Peng JiBin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1039.32
Subject(s) - cotransporter , chemistry , distal convoluted tubule , xenopus , transporter , biophysics , biochemistry , biology , sodium , organic chemistry , nephron , renal function , gene
The Na‐Cl co‐transporter (NCC) and the Ca channel TRPV5 are co‐expressed in the distal convoluted tubule. Our previous studies indicate NCC decreases TRPV5 activity and the enhancing effects of WNK3 and WNK4 on TRPV5. In this study, we aimed at the mechanism by which NCC regulates TRPV5. NCC decreased TRPV5 Ca uptake by 28.5±1.7% when co‐expressed in Xenopus oocytes. This was associated with a decrease in the complexly glycosylated form of TRPV5 at the cell surface. While the C‐terminal regions of NCC had no effect on TRPV5, the N‐terminal regions exhibited moderate effects on TRPV5. In contrast, NCC constructs with the transmembrane domains had robust inhibitory effects on TRPV5 even though most of them exhibited no Na transport activity. Among all NCC constructs tested, the construct containing both N‐terminal and transmembrane domains (aminoacids 1–648) exhibited the strongest effect (43.2±1.8% inhibition). When this construct was co‐expressed, the complexly glycosylated form of TRPV5 was largely absent. As a consequence, the enhancing effects of WNK3 and WNK4 on TRPV5 were completely abolished. A large portion of TRPV5 protein was localized to a region beneath the plasma membrane when NCC or more clearly, the 1–648 construct was co‐expressed. These results suggest that NCC inhibits TRPV5 activity by hindering TRPV5 trafficking to the plasma membrane.