Role of the alternative splice variant of NCC in blood pressure control

Figures

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  Figure 1.. Splicing of NCC gene. Schematic representation of the SLC12A3 gene including exon 20a that encodes for the NCCSV (top). The encoded protein NCC contains 12 transmembrane domains and intracellular amino (N)- and carboxy (C)-terminal domains (bottom). Serine (S811) is highlighted as phosphorylation site in the nine additional amino acids in NCCSV. Left bottom panel shows a multiple protein sequence alignment of the three NCC isoforms, demonstrating the lack of glutamine 95 in NCC2.

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  Figure 2.. Functional role of the novel phosphorylation site serine 811 (S811). The amino (N)-terminal domain of NCC contains several key phosphorylation sites (T55/T66) that are essential for NCC activity and plasma membrane abundance. S811 acts as a dominant regulatory site for phosphorylation of T60 and T55 in NCCSV and NCC3. The various interactions of the NCC regulatory pathway are shown as green arrows (stimulatory) or red lines (inhibitory). Phosphorylation is indicated with the symbol P. The with no lysine kinases (WNKs) are capable of activating SPAK (STE20/SPS1-related, proline alanine-rich kinase) and OSR1 (oxidative stress responsive protein type 1). The hormone receptors are located in the basolateral membrane with indicated signaling pathways involving either serum glucocorticoid regulated kinase 1 (SGK1)-Nedd4-2 pathway, protein kinase A/C (PKA/PKC), or WNKs. V2R, vasopressin receptor; AT1R, angiotensin receptor 1; MR, mineralocorticoid receptor.