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J Membr Biol
2014 Nov 01;24711:1191-7. doi: 10.1007/s00232-014-9719-z.
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SPAK-sensitive regulation of glucose transporter SGLT1.
Elvira B, Blecua M, Luo D, Yang W, Shumilina E, Munoz C, Lang F.
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The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK is a powerful regulator of ion transport. The study explored whether SPAK similarly regulates nutrient transporters, such as the Na(+)-coupled glucose transporter SGLT1 (SLC5A1). To this end, SGLT1 was expressed in Xenopus oocytes with or without additional expression of wild-type SPAK, constitutively active (T233E)SPAK, WNK-insensitive (T233A)SPAK or catalytically inactive (D212A)SPAK, and electrogenic glucose transport determined by dual-electrode voltage-clamp experiments. Moreover, Ussing chamber was employed to determine the electrogenic glucose transport in intestine from wild-type mice (spak(wt/wt)) and from gene-targeted mice carrying WNK-insensitive SPAK (spak(tg/tg)). In SGLT1-expressing oocytes, but not in water-injected oocytes, the glucose-dependent current (I(g)) was significantly decreased following coexpression of wild-type SPAK and (T233E)SPAK, but not by coexpression of (T233A)SPAK or (D212A)SPAK. Kinetic analysis revealed that SPAK decreased maximal I(g) without significantly modifying the glucose concentration required for halfmaximal I(g) (K(m)). According to the chemiluminescence experiments, wild-type SPAK but not (D212A)SPAK decreased SGLT1 protein abundance in the cell membrane. Inhibition of SGLT1 insertion by brefeldin A (5 μM) resulted in a decline of I(g), which was similar in the absence and presence of SPAK, suggesting that SPAK did not accelerate the retrieval of SGLT1 protein from the cell membrane but rather down-regulated carrier insertion into the cell membrane. Intestinal electrogenic glucose transport was significantly lower in spak(wt/wt) than in spak(tg/tg) mice. In conclusion, SPAK is a powerful negative regulator of SGLT1 protein abundance in the cell membrane and thus of electrogenic glucose transport.
Achard,
Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome).
2001, Pubmed
Achard,
Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome).
2001,
Pubmed Alesutan,
Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2.
2012,
Pubmed
,
Xenbase Almilaji,
Down-regulation of Na/K+ atpase activity by human parvovirus B19 capsid protein VP1.
2013,
Pubmed
,
Xenbase Almilaji,
Upregulation of Na+,Cl(-)-coupled betaine/γ-amino-butyric acid transporter BGT1 by Tau tubulin kinase 2.
2013,
Pubmed
,
Xenbase Amador,
Lipopolysaccharide induces inhibition of galactose intestinal transport in rabbits in vitro.
2008,
Pubmed Artunc,
Impaired intestinal and renal glucose transport in PDK-1 hypomorphic mice.
2006,
Pubmed Bogatikov,
Up-regulation of amino acid transporter SLC6A19 activity and surface protein abundance by PKB/Akt and PIKfyve.
2012,
Pubmed
,
Xenbase Capasso,
Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension.
2005,
Pubmed Castañeda-Bueno,
SPAKling insight into blood pressure regulation.
2010,
Pubmed Cheeseman,
Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo.
1997,
Pubmed Dërmaku-Sopjani,
Down-regulation of the Na+-coupled phosphate transporter NaPi-IIa by AMP-activated protein kinase.
2013,
Pubmed
,
Xenbase Dieter,
Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases SGK1, SGK3, and PKB.
2004,
Pubmed
,
Xenbase Ferraris,
Specific regulation of intestinal nutrient transporters by their dietary substrates.
1989,
Pubmed Flatman,
Cotransporters, WNKs and hypertension: an update.
2008,
Pubmed
,
Xenbase Furgeson,
Mechanisms of type I and type II pseudohypoaldosteronism.
2010,
Pubmed Gagnon,
On the substrate recognition and negative regulation of SPAK, a kinase modulating Na+-K+-2Cl- cotransport activity.
2010,
Pubmed
,
Xenbase Giménez,
Molecular mechanisms and regulation of furosemide-sensitive Na-K-Cl cotransporters.
2006,
Pubmed Glover,
SPAK and WNK kinases: a new target for blood pressure treatment?
2011,
Pubmed Glover,
Hypertension, dietary salt intake, and the role of the thiazide-sensitive sodium chloride transporter NCCT.
2011,
Pubmed Henrion,
Overlapping cardiac phenotype associated with a familial mutation in the voltage sensor of the KCNQ1 channel.
2012,
Pubmed
,
Xenbase Hirsh,
Cholecystokinin decreases intestinal hexose absorption by a parallel reduction in SGLT1 abundance in the brush-border membrane.
1998,
Pubmed Hosseinzadeh,
Upregulation of peptide transporters PEPT1 and PEPT2 by Janus kinase JAK2.
2013,
Pubmed
,
Xenbase Hosseinzadeh,
Stimulation of the glucose carrier SGLT1 by JAK2.
2011,
Pubmed
,
Xenbase Hosseinzadeh,
Downregulation of ClC-2 by JAK2.
2012,
Pubmed
,
Xenbase Hosseinzadeh,
Down-regulation of the epithelial Na⁺ channel ENaC by Janus kinase 2.
2014,
Pubmed
,
Xenbase Hosseinzadeh,
Downregulation of KCNQ4 by Janus kinase 2.
2013,
Pubmed
,
Xenbase Huang,
Mechanism of regulation of renal ion transport by WNK kinases.
2008,
Pubmed Ishikawa,
Mechanism of beta-adrenergic agonist-induced transmural transport of glucose in rat small intestine. Regulation of phosphorylation of SGLT1 controls the function.
1997,
Pubmed Kahle,
Phosphoregulation of the Na-K-2Cl and K-Cl cotransporters by the WNK kinases.
2010,
Pubmed Kempe,
Regulation of renal tubular glucose reabsorption by Akt2/PKBβ.
2010,
Pubmed
,
Xenbase Kusche-Vihrog,
Expression of ENaC and other transport proteins in Xenopus oocytes is modulated by intracellular Na+.
2009,
Pubmed
,
Xenbase Lane,
IGF alters jejunal glucose transporter expression and serum glucose levels in immature rats.
2002,
Pubmed Lin,
Impaired phosphorylation of Na(+)-K(+)-2Cl(-) cotransporter by oxidative stress-responsive kinase-1 deficiency manifests hypotension and Bartter-like syndrome.
2011,
Pubmed Loflin,
HuR binds a cyclic nucleotide-dependent, stabilizing domain in the 3' untranslated region of Na(+)/glucose cotransporter (SGLT1) mRNA.
2001,
Pubmed Martín,
Regulation of the human Na(+)-glucose cotransporter gene, SGLT1, by HNF-1 and Sp1.
2000,
Pubmed Mercier-Zuber,
Role of SPAK and OSR1 signalling in the regulation of NaCl cotransporters.
2011,
Pubmed Mia,
Downregulation of Kv1.5 K channels by the AMP-activated protein kinase.
2012,
Pubmed
,
Xenbase Munoz,
Up-regulation of the inwardly rectifying K⁺ channel Kir2.1 (KCNJ2) by protein kinase B (PKB/Akt) and PIKfyve.
2013,
Pubmed
,
Xenbase Nasir,
Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia Senegal).
2010,
Pubmed O'Reilly,
WNK1, a gene within a novel blood pressure control pathway, tissue-specifically generates radically different isoforms with and without a kinase domain.
2003,
Pubmed Pakladok,
PIKfyve sensitivity of hERG channels.
2013,
Pubmed
,
Xenbase Pakladok,
Upregulation of the Na⁺-coupled phosphate cotransporters NaPi-IIa and NaPi-IIb by B-RAF.
2014,
Pubmed
,
Xenbase Pakladok,
Stimulation of the Na(+)-coupled glucose transporter SGLT1 by B-RAF.
2012,
Pubmed
,
Xenbase Pasham,
OSR1-sensitive small intestinal Na+ transport.
2012,
Pubmed Pasham,
OSR1-sensitive regulation of Na+/H+ exchanger activity in dendritic cells.
2012,
Pubmed Pathare,
OSR1-sensitive renal tubular phosphate reabsorption.
2012,
Pubmed
,
Xenbase Pathare,
Enhanced FGF23 serum concentrations and phosphaturia in gene targeted mice expressing WNK-resistant SPAK.
2012,
Pubmed Rafiqi,
Role of the WNK-activated SPAK kinase in regulating blood pressure.
2010,
Pubmed Rexhepaj,
Stimulation of electrogenic glucose transport by glycogen synthase kinase 3.
2010,
Pubmed
,
Xenbase Rexhepaj,
PI3-kinase-dependent electrogenic intestinal transport of glucose and amino acids.
2007,
Pubmed Richardson,
Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways.
2011,
Pubmed Schwab,
Association of SGK1 gene polymorphisms with type 2 diabetes.
2008,
Pubmed Shojaiefard,
Regulation of the Na(+), glucose cotransporter by PIKfyve and the serum and glucocorticoid inducible kinase SGK1.
2007,
Pubmed
,
Xenbase Shojaiefard,
Downregulation of the creatine transporter SLC6A8 by JAK2.
2012,
Pubmed
,
Xenbase Sopjani,
Regulation of Na+-coupled glucose carrier SGLT1 by AMP-activated protein kinase.
2010,
Pubmed
,
Xenbase Stümpel,
Acute increase by portal insulin in intestinal glucose absorption via hepatoenteral nerves in the rat.
1996,
Pubmed Uchida,
Pathophysiological roles of WNK kinases in the kidney.
2010,
Pubmed Ushiro,
Molecular cloning and characterization of a novel Ste20-related protein kinase enriched in neurons and transporting epithelia.
1998,
Pubmed Vayro,
PKC regulates turnover rate of rabbit intestinal Na+-glucose transporter expressed in COS-7 cells.
1999,
Pubmed Veyhl,
Downregulation of the Na(+)- D-glucose cotransporter SGLT1 by protein RS1 (RSC1A1) is dependent on dynamin and protein kinase C.
2003,
Pubmed
,
Xenbase Villa,
Structure of the OSR1 kinase, a hypertension drug target.
2008,
Pubmed Vitari,
The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases.
2005,
Pubmed Warsi,
Effect of Janus kinase 3 on the peptide transporters PEPT1 and PEPT2.
2013,
Pubmed
,
Xenbase Warsi,
Downregulation of chloride channel ClC-2 by Janus kinase 3.
2014,
Pubmed
,
Xenbase Wilson,
Human hypertension caused by mutations in WNK kinases.
2001,
Pubmed Wright,
The sodium/glucose cotransport family SLC5.
2004,
Pubmed Yang,
SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction.
2010,
Pubmed
