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 for the unconventional trafficking of H723R-pendrin.

4 ach the apical compartment in the absence of pendrin.

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

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

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

8 a putative transmembrane protein designated pendrin.

9 ncodes for a putative ion transporter called pendrin.

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

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

12 onventional cell-surface expression of H723R-pendrin.

13 ed 3 chemical classes of inhibitors of human pendrin.

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

15 cell in ultrastructure, but does not express pendrin.

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

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

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

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

20 Wild type pendrin also mediates iodide efflux in transiently trans

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

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

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

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

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

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

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

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

29 Pendrin and prestin both belong to a distinct anion tran

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

47 Pendrin-deficient mice had less allergen-induced airway

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

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

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

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

52 Lack of pendrin during this period led to endolymphatic acidific

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

80 Pendrin inhibition significantly increased ASL depth (by

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

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

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

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

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

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

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

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

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

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

91 Pendrin is closely related to a family of sulfate transp

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

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

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

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

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

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

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

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

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

101 Pendrin-knockout mice show no fluid-electrolyte abnormal

102 Infected pendrin KO mice had higher levels of inflammatory cytoki

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

122 Pendrin/NCC double KO mice displayed severe salt wasting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

159 Pendrin upregulation is associated with PT production by

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

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

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

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

164 Furthermore, pendrin was detected exclusively within the subpopulatio

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

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

167 6.5 to P2 was the critical interval in which pendrin was required for acquisition of normal hearing.

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

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

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

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

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

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

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

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