ライフサイエンスコーパス: podocin

1 ome that included Nphs1 (nephrin) and Nphs2 (podocin).

2 tations in the podocyte gene NPHS2, encoding podocin.

3 tations in the podocyte foot process protein podocin.

4 d desmin, and a recovery of synaptopodin and podocin.

5 foot process junctional markers nephrin and podocin.

6 Mec2, which encodes the homolog of mammalian Podocin.

7 h reduced urinary levels of both nephrin and podocin.

8 e presence of aquaporin-2, polycystin-1, and podocin.

9 decrease in both mRNA and protein levels of podocin, a key component of the slit diaphragm.

10 Podocin accumulates in an oligomeric form in lipid rafts

11 mplicated in the etiology of FSGS, including podocin, alpha-actinin-4, CD2-associated protein (CD2AP)

12 ragm-associated proteins (including nephrin, podocin, alpha-actinin-4, CD2-associated protein, and tr

13 this regard, the human mutations in nephrin, podocin, alpha-actinin-4, COL4A3, and COL4A5 genes expre

14 e kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression.

15 les (and a non-human serum control), nephrin podocin and CD2AP assumed a cytoplasmic distribution; ne

16 n vitro studies reveal direct interaction of podocin and CD2AP.

17 ormal expression levels of podocyte markers, podocin and desmin.

18 ate an intimate relationship between nephrin podocin and filamentous actin, and reason that disruptio

19 ail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but fo

20 Podocin and its Caenorhabditis elegans orthologue MEC-2

21 Although podocin and MEC-2 are membrane-associated proteins with

22 al regulators that control the expression of podocin and nephrin and thereby mediate podocyte differe

23 nd desmin gene expression were increased and podocin and nephrin content were decreased by either the

24 r of podocytes) along with increased urinary podocin and nephrin mRNA excretion, all indicative of gl

25 Urinary podocin and nephrin mRNAs (podocyturia), as candidate bi

26 tial peak of proteinuria and podocyte mRNAs (podocin and nephrin) followed 8 d later by a second peak

27 ficant reduction of slit membrane molecules (podocin and nephrin), key GBM components (fibronectin, l

28 ed reduction in slit diaphragm (SD) proteins podocin and nephrin.

29 It colocalizes with podocin and regulates its stability.

30 modulate expression of Nphs2, which encodes podocin and several other podocyte-expressed genes.

31 -4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact.

32 annel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin

33 regulatory regions of both CD2AP and NPHS2 (podocin) and demonstrated that LMX1B binds to these sequ

34 (cluster of differentiation 45), CD31, CD34, podocin, and albumin were examined by immunohistochemist

35 on the slit diaphragm (SD) proteins nephrin, podocin, and CD2-associated protein (CD2AP) to function

36 stituting molecules (SDCM), such as nephrin, podocin, and CD2-associated protein (CD2AP), were decrea

37 oth unique membrane proteins (e.g., nephrin, podocin, and Neph1) and typical adherens junction protei

38 sses the specific podocyte proteins nephrin, podocin, and synaptopodin were examined by patch clamp.

39 cyte markers Wilms tumor protein 1, nephrin, podocin, and synaptopodin.

40 ferentiation markers (synaptopodin, nephrin, podocin, and WT-1) in HIV-1-infected podocytes.

41 aricalcitol preserved expression of nephrin, podocin, and WT1; prevented proteinuria; and reduced glo

42 ne, the subcellular distribution of nephrin, podocins, and CD2AP and their functional interaction wit

43 PHB2 coprecipitated with podocin, another SPFH domain-containing protein, essenti

44 lar injury associated with increased urinary podocin:aquaporin 2 and nephrin:aquaporin 2 molar ratios

45 ted podocyte detachment (high urinary pellet podocin:aquaporin2 mRNA ratio).

46 lso known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a comp

47 Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial an

48 eover, GST pull-down experiments reveal that podocin associates via its COOH-terminal domain with CD2

49 results in both the correct localization of podocin at the plasma membrane and functional rescue in

50 that the FF diet decreased the expression of podocin but increased desmin and ceramide levels in glom

51 pression of the podocyte markers nephrin and podocin, but there was no loss of cells.

52 cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was on the basis of overexp

53 r genes NPHS1 and NPHS2 encoding nephrin and podocin cause two types of severe nephrotic syndrome pre

54 plasma leads to a concentration of nephrin, podocin, CD2AP, and actin at the cell surface.

55 luding the novel podocyte proteins, nephrin, podocin, CD2AP, and synaptopodin, and known molecules of

56 ns in the same protein complexes as nephrin, podocin, CD2AP, ZO-1, and Neph1 by cosedimentation, coim

57 tations, with sequence variants, and with no podocin changes could not be distinguished from each oth

58 NEPHRIN-PODOCIN colocalization elucidated the variant-specific e

59 idence that podocin R138Q (but not wild-type podocin) complexes with the intermediate filament protei

60 The tracking of single cells in podocin-confetti mice featuring cell-specific expression

61 omology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), l

62 actin, and reason that disruption of nephrin/podocin could be a final common pathway leading to foot

63 The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular e

64 odocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot

65 ated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice).

66 beta1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the tim

67 t mice by crossing beta-PIX floxed mice with Podocin-Cre mice.

68 esangium/pericytes (Foxd1-cre) or podocytes (Podocin-cre) in mice.

69 with that of streptozotocin-induced T1DN in podocin-Cre; Rosa26(fsTRAP); eNOS(-/-) mice using transl

70 analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26(fsTRAP); eNOS(-/-); db/db mice and c

71 Increased urine podocin/creatinine ratio in TG signifies accelerated pod

72 dministration of doxorubicin or an inducible podocin deficiency.

73 Expression of nephrin, podocin, desmin, and transient receptor potential channe

74 tions revealed a role for T234 in regulating podocin dimerization.

75 The T234 site resides at the interface of podocin dimers.

76 e chemical injury or genetic deletion of the podocin-encoding gene Nphs2, the consequent podocyte dam

77 Mutations in NPHS2, the podocin-encoding gene, represent the commonest form of i

78 clampsia associated with an elevated urinary podocin(+) EVs-to-nephrin(+) EVs ratio and may be mediat

79 in-positive to nephrin-positive urinary EVs (podocin(+) EVs-to-nephrin(+) EVs ratio) and increased ne

80 atively correlated with proteinuria, urinary podocin(+) EVs-to-nephrin(+) EVs ratio, and nephrinuria.

81 Immunofluorescence assessed PODOCIN expression and subcellular localization.

82 derm development, as assessed by nephrin and podocin expression in double osr1/sox32-deficient embryo

83 We use our approach to rescue wild-type podocin expression in steroid-resistant nephrotic syndro

84 Ultrastructurally, disruption of nephrin or podocin expression resulted in a loss of slit-diaphragms

85 Moreover, mutant podocin failed to activate the ion channel TRPC6, which

86 The most frequent podocin gene mutation in European children is R138Q, cau

87 Mutations in the human podocin gene NPHS2 cause familial or sporadic forms of r

88 ESRD on 9p21.3, 1q25.1 (in the region of the podocin gene), and 13q33.3.

89 .5-kb fragment derived from the human NPHS2 (podocin) gene was designed in a similar fashion to drive

90 In podocin-GFP mice, podocytes formed sporadic multicellula

91 merular slit diaphragm proteins (nephrin and podocin), glomerular filtration rate, inflammatory and f

92 increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the mi

93 arly expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS

94 AAV-LK03-mediated transduction of podocin in mutant human podocytes resulted in functional

95 ndidate regions for nephrin, CD2AP, WT1, and podocin in this sample.

96 subsets of glomeruli with perturbed nephrin, podocin, integrin alpha3 and fibronectin expression.

97 quitin ligase Ubr4 is a key component of the podocin interactome purified both from cultured podocyte

98 That podocin interacts with CD2AP and nephrin in vivo is show

99 iate-adjusted hazard ratios were highest for podocin, intermediate for nephrin mRNAs, and lowest for

100 The NPHS2 gene product podocin is a key component of the slit diaphragm cell ju

101 Podocin is a key membrane scaffolding protein of the kid

102 Podocin is a key protein of the kidney podocyte slit dia

103 Podocin is expressed in glomerular podocytes, but its su

104 the erythrocyte lipid raft protein stomatin, podocin is present in high-order oligomers and may serve

105 ic analysis of mouse glomeruli revealed that podocin is ubiquitylated at two lysine residues.

106 Its product, podocin, is a new member of the stomatin family, which c

107 podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normot

108 In conditional podocin knockout (KO) mice with severe proteinuria, bloc

109 se amiloride and from mice with proteinuria (podocin knockout [KO]) treated with amiloride or inhibit

110 mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in s

111 Conditional podocin KO in mice led to severe proteinuria and C3a and

112 ogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes.

113 Although wild-type PODOCIN localized to the membrane, distinct variant prot

114 we show, by immunoelectron microscopy, that podocin localizes to the podocyte foot process membrane,

115 phrin), CD2AP, Wilms tumor (WT1), and NPHS2 (podocin) loci.

116 The PHB-domain protein podocin maintains the renal filtration barrier and its m

117 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex

118 lation of one site, K301, do not only target podocin/MEC-2 for proteasomal degradation, but may also

119 y demonstrates that the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of t

120 tored podocyte loss by detecting nephrin and podocin mRNA in urine particulates with quantitative rev

121 In older age podocyte detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at you

122 ratio), podocyte detachment (Urinary pellet podocin mRNA:creatinine ratio: UPPod:CR) and a tubular m

123 peutic option for patients with NS bearing a podocin mutation, with implications for other misfolding

124 of a genotype-phenotype correlation between podocin mutations and age of onset, a worldwide cohort o

125 stant nephrotic syndrome, which is caused by podocin mutations in about 25% of children and nearly 15

126 ngenital nephrotic syndrome with nephrin and podocin mutations resulting from triallelic mutations re

127 Recessive podocin mutations were present in 18.1% (73 of 404) of f

128 han any other patient group, with or without podocin mutations, in this study (mean onset >4.17 yr).

129 podocin mutations, with single heterozygous podocin mutations, with sequence variants, and with no p

130 Patient groups with other recessive podocin mutations, with single heterozygous podocin muta

131 is significantly earlier than for any other podocin mutations.

132 Like Nephrin and Podocin, Neph1 was enriched in Triton X-100 detergent-re

133 on of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced trans

134 ortant podocyte proteins, including those of podocin, nephrin, neph1, alpha-actinin-4, and vimentin.

135 odocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated.

136 r of mTORC1 activation), high urinary pellet podocin:nephrin mRNA ratio and accelerated podocyte deta

137 Podocyte stress (Urinary pellet podocin:nephrin mRNA ratio), podocyte detachment (Urinar

138 Mutations in the gene encoding podocin (NPHS2) cause autosomal recessive steroid-resist

139 We used the human podocin (NPHS2) gene promoter to control expression of t

140 ier revealed that absence of normal nephrin, podocin or mosaic eyes expression results in loss of glo

141 A similar complex with the podocin ortholog MEC-2 is required for touch sensation i

142 the mechanosensory complex that requires the podocin ortholog MEC2 for assembly.

143 To test whether podocin p.R229Q may also predispose to the complex disea

144 The protein podocin p.R229Q, which results from the most common miss

145 Podocin(P118L) and MEC-2(P134S) did not fractionate in d

146 tation that causes kidney disease in humans (podocin(P118L)) has also been identified in C. elegans i

147 lymerization studies showed that nephrin and podocin partially co-localize with actin, most strikingl

148 rstood, critical structural proteins such as podocin play a major role in podocyte survival and funct

149 atenin, accompanied by reduction of nephrin, podocin, podocalyxin, and Wilms tumor 1 proteins.

150 of proteinuria and podocyte mRNAs that were podocin positive but nephrin negative.

151 vesicles, which colocalized with megalin, in podocin-positive cells.

152 amptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podoci

153 ia that persisted for months correlated with podocin-positive, nephrin-negative mRNAs in urine.

154 nvestigate this question, we used the 2.5 kb podocin promoter to target Flag-tagged human vitamin D r

155 t in HIFalpha hyperstabilization, we crossed podocin promoter-Cre transgenic mice, which express Cre

156 Cre-mediated recombination controlled by the podocin promoter.

157 tes under the control of the zebrafish nphs2/podocin promoter.

158 t negative AA-4E-BP1 transgene driven by the podocin promoter; a member of the mammalian target of ra

159 All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription.

160 Podocin protein levels were decreased in Pod(R231Q/wild-

161 in ectatic tubules expressed podocalyxin and podocin proteins but not nephrin, compatible with detach

162 sion and altered localization of nephrin and podocin proteins.

163 Here, we provide evidence that podocin R138Q (but not wild-type podocin) complexes with

164 effect on its own, supporting the concept of podocin R229Q contributing to genetic predisposition in

165 Our findings demonstrate that podocin R231Q exerts a pathogenic effect on its own, sup

166 s in human cultured podocytes expressing the podocin(R231Q) variant.

167 Whereas podocin resides at a specialized cell junction at the po

168 Dual transgenic mice, bearing both podocin-rtTA and tetO-LacZ transgenes, had no detectable

169 On doxycycline induction, podocin-rtTA:tet-O-VEGF164 mice express twofold higher k

170 We postulate that podocin serves in the structural organization of the sli

171 O-1 and alpha-actinin-4, whereas nephrin and podocin solubility were unchanged.

172 ation did not initially affect expression of podocin, synaptopodin, and nephrin but reduced their exp

173 ng mutations of proteins such as nephrin and podocin that are expressed at or near the podocyte slit

174 nephritic syndrome of the Finnish type, and Podocin, the gene mutated in autosomal recessive steroid

175 , claudin-1 interacted with both nephrin and podocin through cis- and trans-associations in cultured

176 and podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio).

177 n of the slit diaphragm proteins nephrin and podocin was decreased, and expression of the transcripti

178 nding to the promoter regions of nephrin and podocin was increased in RA-treated podocytes.

179 addition to membrane expression, nephrin and podocin were detected intracellularly in a filamentous p

180 podocyte proteins synaptopodin, nephrin, and podocin were expressed normally.

181 wever, mRNA and protein levels for CD2AP and podocin were greatly reduced, suggesting a cooperative r

182 Protein levels of EMCN, albumin, and podocin were quantified by Western blot.

183 Zebrafish nephrin and podocin were specifically expressed in pronephric podocy

184 , including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular c

185 The discovery of the genes for nephrin and podocin, which are mutated in two types of congenital ne

186 ced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preser

187 s of podocyte specific proteins, nephrin and podocin within podocytes.