title: SPAK-mediated NCC regulation in response to low-K+ diet.
abstract: The NaCl cotransporter (NCC) of the renal distal convoluted tubule is stimulated by low-K(+) diet by an unknown mechanism. Since recent work has shown that the STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N-terminal sites, we investigated whether the NCC response to low-K(+) diet is mediated by SPAK. Using phospho-specific antibodies in Western blot and immunolocalization studies of wild-type and SPAK knockout (SPAK(-/-)) mice fed a low-K(+) or control diet for 4 days, we found that low-K(+) diet strongly increased total NCC expression and phosphorylation of NCC. This was associated with an increase in total SPAK expression in cortical homogenates and an increase in phosphorylation of SPAK at the S383 activation site. The increased pNCC in response to low-K(+) diet was blunted but not completely inhibited in SPAK(-/-) mice. These findings reveal that SPAK is an important mediator of the increased NCC activation by phosphorylation that occurs in the distal convoluted tubule in response to a low-K(+) diet, but other low-potassium-activated kinases are likely to be involved.
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and jwade@umaryland.edu.
authors: James B
authors: JB
authors: Wade
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors: Jie
authors: J
authors: Liu
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors: Richard
authors: R
authors: Coleman
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors: P Richard
authors: PR
authors: Grimm
authors: Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Eric
authors: E
authors: Delpire
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors: Paul A
authors: PA
authors: Welling
mesh_terms: D000818:Animals; D007686:Kidney Tubules, Distal / Q000201:enzymology*; D018345:Mice, Knockout; D010766:Phosphorylation; D011191:Potassium Deficiency / Q000201:enzymology* / Q000235:genetics; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D064486:Solute Carrier Family 12, Member 3 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D017419:Potassium, Dietary; C578875:Slc12a3 protein, mouse; D064486:Solute Carrier Family 12, Member 3; C486407:Stk39 protein, mouse; C534421:OXSR1 protein, mouse; D017346:Protein Serine-Threonine Kinases
keywords: SPAK; low-K+ diet; renal distal convoluted tubule; sodium chloride cotransporter
references: Proc Natl Acad Sci U S A. 2012 May 15;109(20):7929-34
references: 22550170
references: Am J Physiol Renal Physiol. 2011 Jul;301(1):F14-20
references: 21454253
references: Curr Opin Nephrol Hypertens. 2012 Sep;21(5):516-22
references: 22820370
references: J Biol Chem. 2012 Nov 2;287(45):37673-90
references: 22977235
references: J Am Soc Nephrol. 2013 Feb;24(3):407-18
references: 23393317
references: Kidney Int. 2013 May;83(5):811-24
references: 23447069
references: Am J Physiol Renal Physiol. 2014 May 1;306(9):F1059-68
references: 24598799
references: Sci Signal. 2014 May 6;7(324):ra41
references: 24803536
references: Hypertension. 2014 Jul;64(1):178-84
references: 24799612
references: Am J Physiol Renal Physiol. 2014 Jun 15;306(12):F1507-19
references: 24761002
references: Biosci Rep. 2014;34(3). pii: e00107. doi: 10.1042/BSR20140047
references: 24655003
references: J Biol Chem. 2014 Jun 20;289(25):17680-8
references: 24811174
references: Am J Physiol Renal Physiol. 2000 Nov;279(5):F874-83
references: 11053048
references: Am J Physiol Renal Physiol. 2001 Aug;281(2):F206-12
references: 11457712
references: J Biol Chem. 2002 Dec 27;277(52):50812-9
references: 12386165
references: Am J Physiol Renal Physiol. 2003 Dec;285(6):F1179-87
references: 12952855
references: J Biol Chem. 2003 Dec 26;278(52):52848-56
references: 14563843
references: Kidney Int. 1996 Jun;49(6):1738-42
references: 8743488
references: Biochem J. 2005 Oct 1;391(Pt 1):17-24
references: 16083423
references: Am J Physiol Cell Physiol. 2006 Jan;290(1):C134-42
references: 15930150
references: Mol Cell Biol. 2006 Jan;26(2):689-98
references: 16382158
references: Hypertension. 2006 Feb;47(2):296-308
references: 16434724
references: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1416-20
references: 16434571
references: Nat Genet. 2006 Oct;38(10):1124-32
references: 16964266
references: Am J Physiol Renal Physiol. 2007 Aug;293(2):F541-7
references: 17522262
references: Biochem J. 2008 Jan 15;409(2):321-31
references: 18092945
references: J Cell Sci. 2008 Mar 1;121(Pt 5):675-84
references: 18270262
references: Kidney Int. 2008 Dec;74(11):1403-9
references: 18800028
references: Am J Physiol Renal Physiol. 2009 Sep;297(3):F704-12
references: 19570885
references: EMBO Mol Med. 2010 Feb;2(2):63-75
references: 20091762
references: Am J Physiol Renal Physiol. 2010 Oct;299(4):F890-7
references: 20702602
references: Cell Metab. 2011 Sep 7;14(3):352-64
references: 21907141
references: Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17538-43
references: 21972418
references: Pflugers Arch. 2012 Jun;463(6):853-63
references: 22549242
references: J Biol Chem. 2014 Oct 17;289(42):29273-84
references: 25164821
references: Am J Physiol Renal Physiol. 2012 Jul 1;303(1):F92-104
references: 22496411
references: J Am Soc Nephrol. 2010 Nov;21(11):1868-77
references: 20813865
references: Kidney Int. 2011 Jan;79(1):66-76
references: 20720527
references: J Cell Sci. 2011 Mar 1;124(Pt 5):789-800
references: 21321328
references: Am J Physiol Renal Physiol. 2011 Jun;300(6):F1385-93
references: 21454252
references: Am J Physiol Cell Physiol. 2013 Jan 15;304(2):C147-63
references: 23114965