Na+-K+-2Cl- cotransporter type 2 trafficking and activity: the role of interacting proteins.
The central role of Na+-K+-2Cl- cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and metabolic alkalosis with high prenatal mortality. On the contrary, excessive NKCC2 activity has been linked with inherited hypertension in humans and in rodent models. Interestingly, in animal models of hypertension, NKCC2 upregulation is achieved by post-translational mechanisms underlining the need to analyse the molecular mechanisms involved in the regulation of NKCC2 trafficking and activity to gain insights in the pathogenesis of hypertension.
Department of Biosciences, Biotechnologies and Pharmacological Sciences, University of Bari, Bari, Italy. monica.carmosino@uniba.it
Monica
M
Carmosino
Giuseppe
G
Procino
Maria
M
Svelto
D000818:Animals; D001477:Bartter Syndrome / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D017136:Ion Transport / Q000187:drug effects; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D064466:Solute Carrier Family 12, Member 1; D058949:Uromodulin / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C569026:MAL protein, human; D008565:Membrane Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; C466776:SCAMP2 protein, human; C578714:SLC12A1 protein, human; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; C548612:UMOD protein, human; D058949:Uromodulin; C118135:OXSR1 protein, human; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D005634:Fructose-Bisphosphate Aldolase