Regulation of the renal Na+-Cl- cotransporter by phosphorylation and ubiquitylation.

The activity of the renal thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule plays a key role in defining arterial blood pressure levels. Increased or decreased activity of the NCC is associated with arterial hypertension or hypotension, respectively. Thus it is of major interest to understand the activity of NCC using in vivo models. Phosphorylation of certain residues of the amino-terminal domain of NCC has been shown to be associated with its activation. The development of phospho-specific antibodies against these sites provides a powerful tool that is helping to increase our understanding of the molecular physiology of NCC. Additionally, NCC expression in the plasma membrane is modulated by ubiquitylation, which represents another major mechanism for regulating protein activity. This work presents a review of our current knowledge of the regulation of NCC activity by phosphorylation and ubiquitylation.

The nanopeptide hormone vasopressin is a new player in the modulation of renal Na(+)-Cl(-) cotransporter activity.

Vasopressin is a modulator of salt and water reabsorption, with known effects in the thick ascending limb and the collecting duct. Pedersen et al. present evidence that vasopressin administration increases the phosphorylation of the apical thiazide-sensitive Na(+)-Cl(-) cotransporter in the distal convoluted tubule. These effects appear to be independent of the renin-angiotensin system and to be mediated by the intracellular kinase SPAK. These observations expand the vasopressin-sensitive region of the nephron.