ライフサイエンスコーパス: NHE3

1 ansporters including Na(+)/H(+) exchanger 3 (NHE3).

2 itors or knockdown had an additive effect on NHE3.

3 present at the same time for cGMP to inhibit NHE3.

4 ion was not necessary for cAMP inhibition of NHE3.

5 regulating the post-endosomal fate of human NHE3.

6 to NHE3, while increasing ubiquitination of NHE3.

7 show that glucose exerts a bimodal effect on NHE3.

8 the hormonal stimuli-mediated regulation of NHE3.

9 HE3 aa 690 and of the CaMKII-binding site on NHE3.

10 ecific protease-7 (USP7) and USP10 that bind NHE3.

11 transcellular Na gradient for BBM SGLT1 and NHE3.

12 C-5 plays an essential role in exocytosis of NHE3.

13 transport by redistributing Na/K-ATPase and NHE3.

14 isms by which ClC-5 regulates trafficking of NHE3.

15 ulation of BBM SGLT1 and DRA or PAT1 but not NHE3.

16 and caused redistribution of Na/K-ATPase and NHE3.

17 , and apical plasma membrane localization of NHE3.

18 t increase in co-precipitation of ezrin with NHE3.

19 on of NaCl by targeting Na(+)/H(+) exchanger NHE3.

20 ith PI(4,5)P(2) and PI(3,4,5)P(3) binding of NHE3.

21 on of IRBIT enhanced the effect of ANG II on NHE3.

22 order NHE3 and association between ezrin and NHE3.

23 by interfering with the actions of NHE1 and NHE3.

24 through increased activity of both NHE1 and NHE3.

25 interaction of ezrin with NHERF1, IRBIT, and NHE3.

26 hich are necessary for cGMP/cGKII to inhibit NHE3.

27 ditive effect on PKA-dependent inhibition of NHE3.

28 3, which was associated with reduced surface NHE3.

29 cle), resulting in increased ubiquitinylated NHE3 (+140+/-10%); and decreased NHE3 expression (-50+/-

30 (+250+/-30%, vs. controls), decreased total NHE3 (-23+/-2%), and lowered blood pressure (-24+/-2 mm

31 RNA (3 mug/d, 7 d) increased ubiquitinylated NHE3 (+250+/-30%, vs. controls), decreased total NHE3 (-

32 This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and

33 f NHE3 by effects requiring aa downstream of NHE3 aa 690 and of the CaMKII-binding site on NHE3.

34 Amino acids downstream of NHE3 aa 690 are required for CaMKII to inhibit basal NHE

35 al brush border (BB) Na(+)/H(+) exchanger 3 (NHE3) accounts for most renal and intestinal Na(+) absor

36 investigated the role of IRBIT in mediating NHE3 activation by ANG II.

37 trafficking to the BBM and insulin-dependent NHE3 activation.

38 e endosomal localization of SGK3 and delayed NHE3 activation.

39 One complex stimulates basal NHE3 activity and contains ezrin and phosphoinositides a

40 ion of lysophosphatidic acid (LPA) increased NHE3 activity and fluid absorption in diabetic mice via

41 abetic mice with insulin restored intestinal NHE3 activity and fluid absorption.

42 Dexamethasone (4 h) stimulated wild type NHE3 activity and increased surface expression but faile

43 5 min of ANG II treatment for an increase in NHE3 activity and NHE3 surface expression.

44 these (S515A, S515D, or S526A) reduced basal NHE3 activity and surface expression and had no Akti inh

45 omain of SNX27 is required to maintain basal NHE3 activity and surface expression of NHE3 in polarize

46 A GSK-3 inhibitor reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this ef

47 CaMKII inhibits basal NHE3 activity associated with phosphorylation of NHE3 by

48 NHE3, as well as necessary for inhibition of NHE3 activity by calcium ionophore 4-Br-A23187.

49 es, which are required for the inhibition of NHE3 activity by carbachol.

50 WT mice, whereas the degree of inhibition of NHE3 activity by increasing cellular concentration of cA

51 t component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation; and 3) reduced a

52 SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/o

53 S526D had NHE3 activity equal to wild type with normal Akti inhibi

54 The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further

55 First, NHE3 activity in proximal tubules of wild type (WT) and

56 he effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule.

57 -mediated Na-glucose co-transport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent si

58 tides as major components; how it stimulates NHE3 activity is not known.

59 Basal and dexamethasone-stimulated NHE3 activity of Clcn5 KO mice was decreased compared wi

60 In this study, the roles in regulation of NHE3 activity of these two PBMs were investigated, revea

61 d surface expression but failed to stimulate NHE3 activity or increase surface expression when NHE3 w

62 ependent protein kinase II (CaMKII) inhibits NHE3 activity under basal conditions in intact intestine

63 alpha-MD-G-stimulated jejunal NHE3 activity was defective in NHERF2-/- mice and cells

64 NHE3 activity was measured with 2',7'-bis(carboxyethyl)-

65 NHE3 activity was reduced by an Akti.

66 oses an intracellular pH (pHi) dependence of NHE3 activity, although the biophysical and molecular ba

67 and ERK1/2, reduced Na/K-ATPase activity and NHE3 activity, and caused redistribution of Na/K-ATPase

68 690 are required for CaMKII to inhibit basal NHE3 activity, and mutations of the three putative CaMKI

69 cells expressing NHE3, CaMKII inhibits basal NHE3 activity, because the CaMKII-specific inhibitors KN

70 mulation; and 3) reduced acute inhibition of NHE3 activity-specifically, elevated Ca(2+) related (car

71 e changes in NHE3 activity: 1) reduced basal NHE3 activity-specifically, inhibition of the PI3K/AKT-d

72 sociation of ezrin with NHE3 to affect basal NHE3 activity.

73 ERF3 heterodimerization in the regulation of NHE3 activity.

74 f aa 690 each prevented KN-93 stimulation of NHE3 activity.

75 pecific inhibitors KN-93 and KN-62 stimulate NHE3 activity.

76 4,5)P(2) and PI(3,4,5)P(3) binding and basal NHE3 activity.

77 d binding of IRBIT to NHE3 and its effect on NHE3 activity.

78 m site (S719) that accounts for 40% of basal NHE3 activity.

79 ations in either significantly reduced basal NHE3 activity.

80 S719A but not -S719D had multiple changes in NHE3 activity: 1) reduced basal NHE3 activity-specifical

81 s) toward the acidic side in comparison with NHE3 alone, as measured by oscillating pH electrodes com

82 ccupied by NHERF3 and another ligand such as NHE3, alpha-actinin-4, and PKCalpha, promoting formation

83 CHP1 binding to NHE3 also affected its acute regulation.

84 In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an in

85 It is associated with increased brush-border NHE3 and association between ezrin and NHE3.

86 F2 and in Caco-2/Bbe cells overexpressing HA-NHE3 and cGKII, and in mouse ileum.

87 Mutations were made in the F1 region of NHE3 and cloned in pet30a and pcDNA3.1 vectors.

88 er-74 of IRBIT decreased binding of IRBIT to NHE3 and its effect on NHE3 activity.

89 pamycin inhibition of mTOR reduces levels of NHE3 and Na(+)/H(+) exchange activity in intestinal tiss

90 leton plays an important role in FSS-induced NHE3 and Na/K-ATPase trafficking, and an intact microtub

91 chalasin D blocks the FSS-induced changes in NHE3 and Na/K-ATPase, but not V-ATPase.

92 tools; they also had reduced levels of total NHE3 and NHERF1 compared with control mice.

93 ed well with a change in co-precipitation of NHE3 and NHERF2 but not NHERF1.

94 induction of NS, the increased abundance of NHE3 and phosphorylated NCC in nephrotic mice compared w

95 ound that the expression of Na+/H+ exchanger NHE3 and several scaffold proteins, including NHE3 regul

96 ) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane.

97 employed FRET to study close association of NHE3 and these NHERFs and fluorescence recovery after ph

98 e role of fluid shear stress (FSS) on apical NHE3 and V-ATPase and basolateral Na/K-ATPase traffickin

99 in expression, and a translocation of apical NHE3 and V-ATPase from the intracellular compartment to

100 reabsorption is due to a modulation of both NHE3 and vacuolar H(+)-ATPase (V-ATPase) activity.

101 Cl by the dual operation of Na-H exchange 3 (NHE3) and Cl-HCO(3) [down-regulated in adenoma (DRA) or

102 NKCC2, at Ser552 of the Na(+):H(+) exchanger NHE3, and at Ser552 of beta-catenin.

103 l mouse kidneys significantly affected CFTR, NHE3, and ENaC, altering the cyst phenotype from one poi

104 he interaction and colocalization among D3R, NHE3, and USP48; inhibited USP48 activity (-35+/-6%, vs.

105 nd immunoblotting with specific anti-phospho-NHE3 antibodies.

106 Thus, CHP1 interaction with NHE3 apparently establishes the exchanger set point for

107 hibitors of the Na(+)/H(+) exchanger type 3 (NHE3) are described based on a hit from high-throughput

108 ther or both might dynamically interact with NHE3 as part of Ca(2+) signaling.

109 -2 are localized at the BB, where they bind NHE3 as well as the cytoskeleton, we tested whether eith

110 reen identified sodium hydrogen exchanger 3 (NHE3) as required for efficient multiplication of LCMV i

111 c acid of activity and increased mobility of NHE3, as well as necessary for inhibition of NHE3 activi

112 5) There were some differences in NHE3-associating proteins in the two PBM mutations.

113 ese studies show that phosphorylation of the NHE3 at a single amino acid in the distal part of the C-

114 f NHE3 is associated with phosphorylation of NHE3 at Ser(554), Ser(607), and Ser(663), all of which a

115 exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant ex

116 The conclusions were: 1) NHE3 basal activity is regulated by a signaling complex

117 minal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling.

118 CaMKIIgamma associates with NHE3 between aa 586 and 605 in the NHE3 C terminus in a

119 reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this effect was eliminated in NHE3-S52

120 dies demonstrate that CaMKIIgamma is a novel NHE3-binding protein, and this association is reduced by

121 In conclusion, NHE3 binds to NHERF proteins via both an internal Class

122 man NHE3 by Nedd4-2 regulates endocytosis of NHE3 but does not affect its cellular expression.

123 e and cooperative for dopamine inhibition of NHE3 but reversed that of adenosine.

124 CaMKII inhibits NHE3 by an effect on its turnover number, not changing s

125 HERF2 and does not support the inhibition of NHE3 by carbachol.

126 HERF2 significantly attenuated regulation of NHE3 by Dex but did not completely obliterate the effect

127 study, we compared short-term regulation of NHE3 by Dex in SGK1-null and NHERF2-null mice.

128 Activation of SGK3 and NHE3 by Dex was dependent on phosphoinositide 3-kinase (

129 PS120 cells resulted in robust activation of NHE3 by Dex.

130 factor 2 (NHERF2) and mediates activation of NHE3 by dexamethasone (Dex) in cultured epithelial cells

131 activity associated with phosphorylation of NHE3 by effects requiring aa downstream of NHE3 aa 690 a

132 Ub-conjugation of human NHE3 by Nedd4-2 regulates endocytosis of NHE3 but does n

133 udy tested the hypothesis that cGMP inhibits NHE3 by phosphorylating it and altering its membrane tra

134 2) Dexamethasone stimulates NHE3 by phosphorylation of a single site, Ser(663).

135 internal region (amino acids 586-660) of the NHE3 C terminus and to the NHE3 C-terminal four amino ac

136 CaMKII binding to and phosphorylation of the NHE3 C terminus are parts of the physiologic regulation

137 1) The F1 domain of the NHE3 C terminus has phosphoinositide binding regions.

138 ates with NHE3 between aa 586 and 605 in the NHE3 C terminus in a Ca(2+)-dependent manner, with less

139 Recombinant AKT phosphorylated NHE3 C terminus in the domain ezrin directly binds.

140 SK-3, which act on a Ser cluster in the same NHE3 C-terminal domain that binds ezrin; and 2) these ki

141 s 586-660) of the NHE3 C terminus and to the NHE3 C-terminal four amino acids.

142 His(6) proteins were made from the NHE3 C-terminal region divided into four parts as follow

143 Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a down

144 e we show that SNX27 directly interacts with NHE3 (C-terminus) primarily through the SNX27 PDZ domain

145 sts and polarized Caco-2BBe cells expressing NHE3, CaMKII inhibits basal NHE3 activity, because the C

146 Apical exocytosis of NHE3, CFTR (cystic fibrosis transmembrane conductance re

147 1) Under basal conditions, NHE3 closely associates with NHERF2 in opossum kidney ce

148 Surprisingly, rat NHE3 co-immunoprecipitated Nedd4-2, but its expression a

149 , immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat ren

150 f the C-terminus affects multiple aspects of NHE3 complex formation and changes the NHE3 lipid raft d

151 The S719A mutant had reduced NHE3 complex size, reduced expression in lipid rafts, in

152 CHP1 may serve as a regulatory cofactor for NHE3 conformational change, dependent on intracellular p

153 3) The magnitude of serum stimulation of NHE3 correlates with PI(4,5)P(2) and PI(3,4,5)P(3) bindi

154 Loss of mTOR regulation of NHE3 could mediate the development of diarrhea in patien

155 Second, NHE3-dependent absorption of HCO(3)(-), measured by sing

156 of ClC-5, whereas the total protein level of NHE3 did not change.

157 NHE3 directly binds Na(+)/H(+) exchanger regulatory fact

158 NHE3 distribution was assessed by cell-surface biotinyla

159 orylation of Na(+)/H(+) exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvill

160 by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose.

161 Under basal conditions, NHERF2 and NHE3 exhibited robust FRET signaling.

162 Na(+)/H(+) exchanger NHE3 expressed in the intestine and kidney plays a major

163 g/min, 4 d) in C57Bl/6J mice increased renal NHE3 expression (+310+/-15%, vs. vehicle), whereas an in

164 uitinylated NHE3 (+140+/-10%); and decreased NHE3 expression (-50+/-9%) in human renal proximal tubul

165 n between D3R and USP48 in the regulation of NHE3 expression and function.

166 increased NHE3 ubiquitination and decreased NHE3 expression at the surface membrane and cellular lev

167 onstituted these macrocomplexes and restored NHE3 expression in the BBM.

168 blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflam

169 d to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na(+) absorption is

170 2) and Arg(520)-Arg(552)) are present in the NHE3 F1 domain; both regions are important for serum sti

171 4,5)P(2) and PI(3,4,5)P(3) bound only to the NHE3 F1 fusion protein (amino acids 475-589) on liposoma

172 quirement for three phosphorylation sites in NHE3 for cGKII inhibition, and for phosphorylation of on

173 min of A23187 (0.5 mum) exposure, the NHERF2-NHE3 FRET signal was abolished, and BB NHE3 mobility was

174 t1/2=21.8 h), indicating that USP48 protects NHE3 from degradation via deubiquitinylation.

175 ired for the exocytosis (not endocytosis) of NHE3 from early endosome to plasma membrane.

176 pendent; was associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile frac

177 ) abrogated the inhibitory effect of cAMP on NHE3 function via an IP(3) receptor-dependent mechanism.

178 d intracellular Ca(2+), we hypothesized that NHE3 had to be, at least transiently, released from the

179 ), whereas overexpression of USP48 increased NHE3 half-life (t1/2=21.8 h), indicating that USP48 prot

180 internal PBM mutation but no change in total NHE3 half-life in either.

181 In addition, NHE3 half-life was reduced accounting for decreased NHE3

182 However, there is a paradox in that NHE3 has limited mobility in the BB due to its binding t

183 We found that Nedd4-2 ubiquitinated human NHE3 (hNHE3) and altered its expression and activity.

184 ovel endosomal kinase that acutely regulates NHE3 in a PI3K-dependent mechanism.

185 r, these findings indicate the importance of NHE3 in diabetic diarrhea and suggest LPA administration

186 of low doses of rapamycin reduced levels of NHE3 in intestinal tissues; this effect was not observed

187 ant reduction in half-life of the PM pool of NHE3 in only the internal PBM mutation but no change in

188 asal NHE3 activity and surface expression of NHE3 in polarized epithelial cells.

189 ssociated with reduced surface expression of NHE3 in proximal tubules.

190 e analysis showed that SGK3 colocalized with NHE3 in recycling endosomes, whereas SGK1 and SGK2 were

191 and consequent regulation of Na/K-ATPase and NHE3 in renal proximal tubule may contribute to salt-ind

192 nd induced redistribution of Na/K-ATPase and NHE3 in renal proximal tubules.

193 naling and redistribution of Na/K-ATPase and NHE3 in the Dahl R rats, but not in the Dahl S rats.

194 ads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependen

195 rmation about the function and regulation of NHE3 (including its role in regulating paracellular Ca2+

196 Indeed, CHP1 interaction with NHE3 inhibited NHE3 transport in a pHi -dependent manner

197 ture of 13d then provided 3D-QSAR models for NHE3 inhibition capturing guidelines for optimization.

198 nd expression, and reveal a new mechanism of NHE3 inhibition involving DUBs.

199 ent Na(+) absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in n

200 f potent, selective, and orally bioavailable NHE3 inhibitors with 13d as best compound, showing high

201 y, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.

202 o multiple proteins that bind throughout the NHE3 intracellular C-terminus, including calcineurin hom

203 epithelial brush-border Na(+)/H(+) exchanger NHE3 is acutely inhibited by cGKII/cGMP, but how cGKII i

204 We conclude that 1) cGMP inhibition of NHE3 is associated with phosphorylation of NHE3 at Ser(5

205 NHE3 is inhibited by protein kinase A.

206 This overall phosphorylation of NHE3 is not affected by the presence of NHERF2.

207 Back phosphorylation demonstrated that NHE3 is phosphorylated by CaMKII under basal conditions.

208 The brush border (BB) Na(+)/H(+) exchanger NHE3 is rapidly activated or inhibited by changes in tra

209 ibited by cGKII/cGMP, but how cGKII inhibits NHE3 is unknown.

210 Na(+)/H(+) exchanger 3 (NHE3) is present in pkd1-knockout and normal mice and in

211 Na(+)/H(+) exchanger 3 (NHE3) is the major Na(+) transporter in the intestine.

212 these sites for dexamethasone stimulation of NHE3, is a unique example of regulation by phosphorylati

213 vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links

214 binding phosphoprotein of 50 kDa (EBP50) and NHE3 kinase A regulatory protein (E3KARP) both consist o

215 ts of NHE3 complex formation and changes the NHE3 lipid raft distribution, which cause changes in spe

216 heterodimerization mediates the formation of NHE3 macrocomplexes, which are required for the inhibiti

217 inin-4, and PKCalpha, promoting formation of NHE3 macrocomplexes.

218 as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset

219 minal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption.

220 Lumen butyrate-Ringer incubation activated NHE3-mediated Na(+) absorption in DSS-induced colitis.

221 ether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal

222 e observations indicate that in normal colon NHE3 mediates both HCO3 (-)-dependent and butyrate-depen

223 n of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and was acco

224 The dynamics in FRET signal and NHE3 mobility correlated well with a change in co-precip

225 nce recovery after photobleaching to monitor NHE3 mobility in the apical domain in polarized opossum

226 HERF2-NHE3 FRET signal was abolished, and BB NHE3 mobility was transiently increased.

227 n and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal.

228 All mutations were in the NHE3 N-terminal transport domain, and all missense mutat

229 Molecular analysis revealed that NHE3, NHERF1, IRBIT, and ezrin form macrocomplexes, whic

230 3) The change in NHE3-NHERF2 association is accompanied by an increased B

231 of elevated Ca(2+), the close association of NHE3-NHERF2 is abolished but is re-established in approx

232 ased the abundance of total and cell-surface NHE3, NKCC2, NCC, alpha-ENaC and cleaved gamma-ENaC comp

233 At day 3, the abundance of NHE3 normalized, phosphorylated NCC levels decreased, an

234 Na(+) /H(+) exchanger NHE3 of human or primates differs from NHE3 of other ani

235 anger NHE3 of human or primates differs from NHE3 of other animals by having a PY motif, which mediat

236 s also required to regulate the retention of NHE3 on the plasma membrane.

237 also altered the location of CFTR but not of NHE3 or ENaC in normal mice.

238 .003) as were all NHE genes (NHE1, NHE2, and NHE3; P < 0.05).

239 hough the biophysical and molecular basis of NHE3 pHi sensitivity have not been defined.

240 cGMP/cGKII increased NHE3 phosphorylation at three sites (rabbit Ser(554), Se

241 Identification of NHE3 phosphorylation sites was by iTRAQ/LC-MS/MS with Ti

242 lf-life was reduced accounting for decreased NHE3 protein abundance.

243 Total and percent plasma membrane (PM) NHE3 protein expression was reduced in the C-terminal bu

244 Insertion of a PY motif in rabbit NHE3 recapitulated the interaction with Nedd4-2 and enha

245 astrointestinal sodium/hydrogen exchanger 3 (NHE3), reduces paracellular phosphate transport.

246 HERF2 domain was functionally significant in NHE3 regulation, being necessary for stimulation by lyso

247 oteins that are required for many aspects of NHE3 regulation.

248 HE3 and several scaffold proteins, including NHE3 regulatory factors (NHERFs), inositol trisphosphate

249 asal activity of the BB Na(+)/H(+) exchanger NHE3 requires multiprotein complexes that form on its C

250 USP48 silencing decreased NHE3's half-life (USP48 siRNA t1/2=6.1 h vs. vehicle t1/

251 be cells was further examined by mutation of NHE3-S(719) to A (not phosphorylated) or D (phosphomimet

252 NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had

253 NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound e

254 3 binding, and this effect was eliminated in NHE3-S526A and -S526D mutants.

255 ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound ezrin normally.

256 NHE3-S719A but not -S719D had multiple changes in NHE3 a

257 A comparison of NHE3 sequences revealed the presence of PY motifs in NHE

258 NHE3-Ser(526) is predicted to be a GSK-3 kinase phosphor

259 NHE3-Ser(663) phosphorylation was not necessary for cAMP

260 ssion of gamma-epithelial sodium channel and NHE3 (sodium-hydrogen antiporter 3).

261 The former determines NHE3 stability in the PM, and the latter determines tota

262 RF1 knockdown; was associated with increased NHE3 surface expression in Caco-2 cells, which also was

263 Parathyroid hormone decreased NHE3 surface expression, but the extent of decrease and

264 ng, and the latter but not the former alters NHE3 surface expression.

265 eatment for an increase in NHE3 activity and NHE3 surface expression.

266 s are parts of the physiologic regulation of NHE3 that occurs in fibroblasts as well as in the BB of

267 gulate the dynamic association of ezrin with NHE3 to affect basal NHE3 activity.

268 tion of the isoform 3 Na(+)/H(+) antiporter (NHE3) to demonstrate a functional relevance for CO(2)-me

269 Silencing of NHERF1 or IRBIT prevented NHE3 trafficking to the BBM and insulin-dependent NHE3 a

270 of NHE3, which contributes to inhibition of NHE3 transport activity via increased endocytosis.

271 physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic gluco

272 Indeed, CHP1 interaction with NHE3 inhibited NHE3 transport in a pHi -dependent manner.

273 Epithelial Na(+)/H(+) exchanger-3 (NHE3) transport is fundamental for renal and intestinal

274 kdown of USP7 or USP10 resulted in increased NHE3 ubiquitination and decreased NHE3 expression at the

275 e that USP7 and USP10 are DUBs that regulate NHE3 ubiquitination and expression, and reveal a new mec

276 d the hypothesis that phosphoinositides bind NHE3 under basal conditions and are necessary for its ac

277 ANG II-induced activation of NHE3 was abrogated by knockdown of IRBIT, whereas overex

278 Surface NHE3 was determined by cell surface biotinylation.

279 y cell surface biotinylation, trafficking of NHE3 was examined in short hairpin RNA (shRNA) plasmid-t

280 h contributed to the altered distribution of NHE3 was examined.

281 3) cGMP- and Ca(2+)-mediated inhibition of NHE3 was impaired in both the internal and the C-termina

282 is effect was eliminated if ezrin binding to NHE3 was inhibited by a point mutant.

283 activity or increase surface expression when NHE3 was mutated to either S663A or S663D.

284 The endocytic retrieval of NHE3 was promoted by depletion of USP7 or USP10, with in

285 Surface NHE3 was reduced in opossum kidney cells with reduced ex

286 The expression of NHE3 was reduced in the ileal brush border of patients w

287 Ezrin binding to NHE3 was regulated by Akt, being eliminated by Akti.

288 lation of BBM SGLT1 and DRA or PAT1, whereas NHE3 was unaffected.

289 ification to reduce the CHP1 amount bound to NHE3) was permissive and cooperative for dopamine inhibi

290 l and dexamethasone-stimulated exocytosis of NHE3 were attenuated in ClC-5 knockdown cells.

291 The roles of DUBs in regulation of NHE3 were studied by determining the effects of silencin

292 Levels of the Na+/H+ exchanger 3 (NHE3) were measured in human ileal biopsy specimens from

293 NHE3, when complexed with the calcineurin homologous pro

294 SLC9A3 encodes Na(+)/H(+) antiporter 3 (NHE3), which is the major intestinal brush-border Na(+)/

295 panied by an increased BB mobile fraction of NHE3, which contributes to inhibition of NHE3 transport

296 cGMP/cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

297 n decreased the binding of USP7 and USP10 to NHE3, while increasing ubiquitination of NHE3.

298 IRBIT facilitated the interaction of NHE3 with NHERF1 via protein kinase D2-dependent phospho

299 USP7 or USP10, with increased association of NHE3 with Rab5a and Rab7.

300 unlike SGK1 or SGK2, SGK3 rapidly activated NHE3 within 15 min of Dex treatment in both PS120 and Ca