ライフサイエンスコーパス: pendrin

1 ing the function of the PDS-encoded protein (pendrin).

2 ene and the function of its encoded protein (pendrin).

3 ) concentration, [HCO(3)(-)], independent of pendrin.

4 cell in ultrastructure, but does not express pendrin.

5 ach the apical compartment in the absence of pendrin.

6 tations in the PDS/SLC26A4 gene that encodes pendrin.

7 members of the SLC26 family DRA, SLC26A6 and pendrin.

8 albeit at a much lower level than wild-type pendrin.

9 a putative transmembrane protein designated pendrin.

10 ncodes for a putative ion transporter called pendrin.

11 1, where there was a significant decrease in pendrin.

12 uctures at the C-terminus of human and mouse pendrin.

13 ding dogma of the electroneutral activity of pendrin.

14 onventional cell-surface expression of H723R-pendrin.

15 ed 3 chemical classes of inhibitors of human pendrin.

16 for the unconventional trafficking of H723R-pendrin.

17 ding Slc26a3/Dra, Slc26a6/Pat-1, and Slc26a4/pendrin.

18 teral secretin receptors and apical CFTR and pendrin.

19 less active in the airways in the absence of pendrin.

20 s a molecular ruler, our studies reveal that pendrin, a clinically relevant anion transporter in the

21 e regulation, the most important of which is pendrin, a luminal Cl/HCO(3)(-) exchanger.

22 In contrast, WNK4 showed no inhibition of pendrin, a related Cl(-)/base exchanger.

23 ressed sequence tag database for homologs of pendrin, a transporter previously shown to mediate Cl(-)

24 age, epithelial sodium channel activity, and pendrin abundance and subcellular distribution in wild-t

25 abundance in the apical membrane region and pendrin abundance per cell whether serum potassium was h

26 Pendrin activation and ATP12A inhibition could represent

27 educed, and beta2 -adrenergic stimulation of pendrin activity was blunted in ATP6v1b1-/- mice.

28 ecting ducts in CFTR knockout mice, baseline pendrin activity was significantly lower and not respons

29 At least in some treatment models, pendrin acts in tandem with the Na(+)-dependent Cl(-)/HC

30 Pendrin also exports iodide (I(-)) in the thyroid gland.

31 Wild type pendrin also mediates iodide efflux in transiently trans

32 SLC26A4 encodes pendrin, an anion-base exchanger expressed in inner ear

33 17 markedly increased ASL pH by upregulating pendrin, an apical Cl-/HCO3- exchanger.

34 secretes HCO(3) by an apical Cl:HCO(3) named pendrin and a basolateral vacuolar (V)-ATPase.

35 m express the luminal Cl - /HCO 3- exchanger pendrin and apical and/or basolateral H + -ATPases conta

36 e are canonical beta-type cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase.

37 This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFT

38 Although pendrin and ENaC localize to different cell types, ENaC

39 use intracellular trafficking regulates both pendrin and H(+)-ATPase, we hypothesized that AngII indu

40 membrane, whereas the beta-subtype expresses pendrin and localizes the H(+)v-ATPase cytosolically or

41 We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen wi

42 We hypothesized that pendrin and NCC compensate for loss of function of the o

43 Pendrin and prestin both belong to a distinct anion tran

44 te the amino acid sequence disparity between pendrin and prestin.

45 protein show moderate sequence similarity to pendrin and related sulphate/anion transport proteins.

46 independent cell-surface expression of H723R-pendrin and restored its cell-surface Cl(-)/HCO3(-) exch

47 vitro, and the subcellular distributions of pendrin and the H(+)-ATPase were quantified using immuno

48 lel operation of the Cl(-)/HCO3(-) exchanger pendrin and the Na(+)-driven Cl(-)/2HCO3(-) exchanger (N

49 tions, although mice with double knockout of pendrin and the Na(+)/Cl(-) cotransporter (NCC) manifest

50 ent protein (GFP) chimeras of wild-type (WT) pendrin and three common natural mutants (L236P, T416P a

51 bonate secretion involving CFTR and SLC26A4 (pendrin) and a persistent proton secretion by ATP12A.

52 Targeting three distinct proteins, NhaA, pendrin, and the Plasmodium falciparum chloroquine resis

53 s of the Cl(-)/HCO(-)(3) antiporters ae1 and pendrin, and two isoforms of carbonic anhydrase.

54 Inhibitors of pendrin anion exchange identified in a small molecule sc

55 Mutations in SLC26A4, which encodes pendrin, are responsible for hearing loss with an enlarg

56 consistent with the putative functioning of pendrin as an anion transporter.

57 e (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases S

58 determine if the receptor directly regulates pendrin, as well as the effect of serum aldosterone and

59 Here we show that H723R-pendrin can be rescued to the cell surface by an HSP70 c

60 provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new a

61 Mutations in the transmembrane protein, pendrin, cause diminished export of iodide from thyroid

62 Instead, pendrin changes ENaC abundance and function at least in

63 -stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness,

64 Pendrin-deficient mice had less allergen-induced airway

65 -induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydratio

66 rtical collecting ducts, secretin stimulated pendrin-dependent Cl(-)/HCO(3) (-) exchange.

67 We gave aldosterone and NaHCO(3) to increase pendrin-dependent HCO(3)(-) secretion within the connect

68 tercalated cells (IC) via an H(+)-ATPase-and pendrin-dependent mechanism.

69 Moreover, excessive chloride absorption by pendrin drove parallel absorption of sodium through the

70 Lack of pendrin during this period led to endolymphatic acidific

71 toward the fate of the immediately adjacent Pendrin-expressing epithelial cells.

72 ad higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced le

73 atory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammat

74 Total pendrin expression and activity in non-type A ICs of ex

75 ldosterone and angiotensin II also stimulate pendrin expression and function, which likely contribute

76 In this study, we found that pendrin expression is upregulated at both gene and prote

77 nesulfonamide compounds reversibly inhibited pendrin-facilitated Cl(-) exchange with SCN(-), I(-), NO

78 These studies implicate the involvement of pendrin-facilitated Cl(-)/HCO3 (-) in the regulation of

79 ansmembrane conductance regulator (CFTR) and pendrin for normal function [P.

80 ectron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl(-),

81 ral membrane protein, VSVGtsO45 or wild-type pendrin from targeting the plasma membrane.

82 ice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collectin

83 We propose a model for pendrin function in the thyroid in which pendrin transpo

84 The reduced pendrin function, along with a compensatory upregulation

85 Our results demonstrate that pendrin functions as a transporter of chloride and iodid

86 ng its putative second transmembrane domain, pendrin has been proposed to function as a sulfate trans

87 now report the cDNA cloning of CFEX, a mouse pendrin homolog with expression in the kidney by Norther

88 We also determine the structure of pendrin in a complex with niflumic acid (NFA), which unc

89 cantly increased following the expression of pendrin in both cell systems.

90 contribution of the Cl(-)/HCO3(-) exchanger pendrin in distal nephron function.

91 drin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic

92 st steps toward defining the precise role of pendrin in inner ear development and elucidating the pat

93 mice overexpressing the chloride transporter pendrin in intercalated cells of the distal nephron (Tg(

94 ndred's syndrome suggests a possible role of pendrin in iodide transport at the apical membrane of th

95 Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibitio

96 Although a role for pendrin in maintaining Na(+) balance, intravascular volu

97 ximity to the chloride-absorbing transporter pendrin in the kidney distal nephron.

98 dy examined the distribution and function of pendrin in the mammalian kidney.

99 ulfate transport following the expression of pendrin in Xenopus laevis oocytes by microinjection of P

100 C, did not change, although the abundance of pendrin increased in these mice.

101 asing distal delivery of HCO(3)(-) through a pendrin-independent mechanism "rescues" ENaC function in

102 with Pendred syndrome have complete loss of pendrin-induced chloride and iodide transport, while all

103 le of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the

104 Pendrin inhibition in WT airways recapitulated the CF ai

105 Pendrin inhibition significantly increased ASL depth (by

106 (-) exchange and the increase was blocked by pendrin inhibition.

107 therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput scre

108 Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in in

109 ockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mi

110 ion of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, includ

111 Pendrin is a Cl(-)/HCO3(-) exchanger expressed in type B

112 Pendrin is a Na(+)-independent Cl(-)/HCO3(-) exchanger t

113 Functionally, pendrin is a transporter of chloride and iodide in Xenop

114 Inhibition of pendrin is a validated approach for attenuating airway h

115 Pendrin is an anion transporter encoded by the PDS/Pds g

116 Together, these studies indicate that pendrin is an apical anion transporter in intercalated c

117 Pendrin is closely related to a family of sulfate transp

118 Studies of Slc26a4-null mice indicate that pendrin is essential for inner ear development, but have

119 Previously, we showed that pendrin is expressed in ameloblasts but is not critical

120 ion of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13.

121 -ATPase but not aquaporin-2, indicating that pendrin is present in intercalated cells of the CCD.

122 r development, but have not revealed whether pendrin is specifically necessary for homeostasis.

123 rcalated cell chloride/bicarbonate exchanger pendrin is unclear, as are potassium's role in this resp

124 ed long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increa

125 SLC26A4 (Pendrin) is necessary for normal reabsorption of endolym

126 The predicted protein, pendrin, is closely related to a number of known sulphat

127 B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loa

128 uences of acute oral base loading in normal, pendrin knockout (KO), and CFTR KO mice.

129 Studies using pendrin knockout mice and airway epithelial cells from h

130 Pendrin-knockout mice show no fluid-electrolyte abnormal

131 Infected pendrin KO mice had higher levels of inflammatory cytoki

132 in/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice.

133 In contrast, CFTR and pendrin KO mice, which are unable to rapidly excrete exc

134 and potassium on this response, we measured pendrin label intensity and subcellular distribution in

135 s syndrome, naturally occurring mutations of pendrin lead to impaired transport of iodide.

136 al cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin

137 Thus, pendrin may attenuate diuretic-induced salt loss, but th

138 Therefore, pendrin may represent a novel therapeutic target for tre

139 el, ENaC, and the Cl(-)/HCO(3)(-) exchanger, pendrin, mediate NaCl absorption within the cortical col

140 The pendrin-mediated Cl(-)/HCO3(-) exchange process is great

141 tion and HCO3(-) secretion primarily through pendrin-mediated Cl(-)/HCO3(-) exchange.

142 These results provide evidence that pendrin mediates apical iodide efflux from polarized mam

143 Because pendrin mediates HCO(3)(-) secretion, we asked if increa

144 In cells expressing NIS and pendrin, pendrin mediates transport of iodide into the apical cha

145 To determine whether pendrin might also play a role in virus-induced exacerba

146 Pendrin modulates aldosterone-induced Na(+) absorption b

147 We conclude that pendrin modulates ENaC abundance and function, at least

148 induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally

149 In contrast, both pendrin mutants lose the ability to promote iodide efflu

150 n and defective plasma membrane targeting of pendrin mutants play a key role in the pathogenesis of P

151 Pendrin mutations in humans lead to Pendred syndrome, ca

152 the epithelial sodium channel (ENaC) and the pendrin/Na(+)-driven chloride/bicarbonate exchanger (pen

153 To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendri

154 Pendrin/NCC double KO mice displayed severe salt wasting

155 Na(+)-driven chloride/bicarbonate exchanger (pendrin/NDCBE) transport system was impaired.

156 In the absence of pendrin [Slc26a4 (-/-) or pendrin null mice], aldosterone-stimulated NaCl absorpti

157 ubunit abundance and function was similar in pendrin-null and wild-type mice.

158 ing treatment with aldosterone and NaHCO(3), pendrin-null mice had lower urinary pH and [HCO(3)(-)] a

159 nd activity are lower in aldosterone-treated pendrin-null mice relative to wild-type mice.

160 pendent mechanism "rescues" ENaC function in pendrin-null mice.

161 studies detected expression of CFEX, but not pendrin, on the brush border membrane of proximal tubule

162 kalization, an effect absent in mice lacking pendrin or CFTR.

163 in vitro did not change the distribution of pendrin or H(+)-ATPase within type B IC but within type

164 Single deletion of pendrin or NCC does not cause salt wasting or excessive

165 xpressing the sodium iodide symporter (NIS), pendrin, or NIS and pendrin using a bicameral system-per

166 Our data show that ameloblasts express Dra, pendrin, or Slc26a6 but each of these separately is not

167 ncoding connexin-26, myosin VIIA, myosin XV, pendrin, otoferlin and alpha-tectorin, respectively.

168 In cells expressing NIS and pendrin, pendrin mediates transport of iodide into the a

169 lude that the chloride/bicarbonate exchanger pendrin plays a major role in controlling net NaCl absor

170 Herein we show that pendrin plays a role in allergic airway disease and in r

171 calization studies were performed using anti-pendrin polyclonal and monoclonal antibodies.

172 n AE1-positive A-type and decreased pH(i) in pendrin-positive B-type of intercalated cells.

173 isoforms, and V-type H(+)-ATPase subunits in pendrin-positive intercalated cells (PP-ICs) and ENaC su

174 enamel organs of Slc26a6-null mice, Dra and pendrin protein levels were both elevated by 52% and 55%

175 uptake measurements showed that the chimeric pendrin protein retained the capability to transport for

176 whether it was possible to create a chimeric pendrin protein with motor capability by integrating thi

177 We conclude that pendrin regulates ASL thickness and may be an important

178 coid receptor gene ablation directly reduced pendrin's relative abundance in the apical membrane regi

179 This receptor directly regulates pendrin's total abundance and its relative abundance in

180 albindin-D28k, H(+)-ATPase, aquaporin-2, and pendrin showed that distal convoluted tubule and connect

181 minal green fluorescent protein (GFP)-tagged pendrin (SLC26A4) construct, whereas cells transfected w

182 minal green fluorescent protein (GFP)-tagged pendrin (SLC26A4) construct.

183 Pendrin (SLC26A4) is a chloride-iodide transporter that

184 Pendrin (SLC26A4) is a Cl(-)/anion exchanger expressed i

185 Pendrin (SLC26A4) is an anion exchanger that mediates bi

186 ression and impaired apical translocation of pendrin (Slc26A4) were causative for the augmented urina

187 yrocytes solely via the Cl(-)/I(-) exchanger Pendrin (SLC26A4), therefore necessitating reconsiderati

188 In the absence of pendrin [Slc26a4 (-/-) or pendrin null mice], aldosteron

189 ung inflammatory pathology without affecting pendrin synthesis or bacterial loads.

190 the combined inhibition of NCC and the NDCBE/pendrin system may explain thiazide-induced hypokalemia

191 hing (FRAP) studies demonstrated that GFP-WT pendrin targets to the plasma membrane.

192 icarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology.

193 The expression of pendrin, the water channel AQP2, and subunits of the epi

194 Aldosterone regulates pendrin through mechanisms both dependent and independen

195 t did not eliminate, aldosterone's effect on pendrin total and apical abundance and subcellular distr

196 restin function, were measured from chimeric pendrin-transfected human embryonic kidney 293 cells usi

197 1, NaPi2) and higher distal (NCC, ENaC, and pendrin) transporter abundance, a pattern facilitating K

198 for pendrin function in the thyroid in which pendrin transports iodide across the apical membrane of

199 To clarify the physiologic role of pendrin under conditions not confounded by gene knockout

200 IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl(-)/HCO3 (-)

201 Pendrin upregulation is associated with PT production by

202 iodide symporter (NIS), pendrin, or NIS and pendrin using a bicameral system-permitting measurement

203 Thus, the engineered pendrin was capable of both transporting anions and gene

204 The chimeric pendrin was constructed by substituting residues 160-179

205 c26a4-null background so that all functional pendrin was derived from the transgenes.

206 Furthermore, pendrin was detected exclusively within the subpopulatio

207 However, pendrin was not detected in kidneys from a Pds-knockout

208 The same distribution of pendrin was observed in mouse, rat, and human kidney.

209 6.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing.

210 ner-ear defects that occur in the absence of pendrin, we have generated a Pds-knockout mouse.

211 The iodide transport properties of pendrin were determined in polarized Madin-Darby canine

212 In contrast, all three mutant pendrins were retained in the endoplasmic reticulum (ER)

213 ne encodes a transmembrane protein, known as pendrin, which functions as a transporter of iodide and

214 tussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory

215 bited Cl(-)/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1-3 micro

216 ed by substituting residues 160-179 in human pendrin with residues 156-169 from gerbil prestin.

217 substitution from prestin was able to confer pendrin with voltage-dependent motor capability despite