A SPAK isoform switch modulates renal salt transport and blood pressure.
Cell Metab
; 14(3): 352-64, 2011 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-21907141
The renal thick ascending limb (TAL) and distal convoluted tubule (DCT) play central roles in salt homeostasis and blood pressure regulation. An emerging model suggests that bumetanide- and thiazide-sensitive NaCl transporters (NKCC2 and NCC) along these segments are phosphorylated and activated by WNK kinases, via SPAK and OSR1. Here, we show that a kidney-specific SPAK isoform, which lacks the kinase domain, inhibits phosphorylation of NCC and NKCC2 by full-length SPAK in vitro. Kidney-specific SPAK is highly expressed along the TAL, whereas full-length SPAK is more highly expressed along the DCT. As predicted from the differential expression, SPAK knockout in animals has divergent effects along TAL and DCT, with increased phosphorylated NKCC2 along TAL and decreased phosphorylated NCC along DCT. In mice, extracellular fluid volume depletion shifts SPAK isoform abundance to favor NaCl retention along both segments, indicating that a SPAK isoform switch modulates sodium avidity along the distal nephron.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Equilibrio Hidroelectrolítico
/
Presión Sanguínea
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Cloruro de Sodio
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Proteínas Serina-Treonina Quinasas
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Líquido Extracelular
/
Isoenzimas
/
Túbulos Renales Distales
/
Asa de la Nefrona
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos