ライフサイエンスコーパス: paranodal

1 s a pivotal role in interactions between the paranodal AGSJs and axonal cytoskeleton, and that 4.1B i

2 Caspr and Caspr2, which localize at paranodal and juxtaparanodal domains, contain binding si

3 of the nodes of Ranvier as a linker between paranodal and juxtaparanodal membrane proteins to the sp

4 ns the molecular components of normal nodes; paranodal and juxtaparanodal proteins are properly local

5 des fragment and disappear, glial and axonal paranodal and juxtaparanodal proteins no longer cluster,

6 Our results demonstrate that ECM, paranodal, and axonal cytoskeletal mechanisms ensure rob

7 ch included the development of mature nodal, paranodal, and juxtaparanodal domains, as assessed by ul

8 on the molecular organization of the nodal, paranodal, and juxtaparanodal region, reflecting altered

9 of key molecules that make up the nodal and paranodal apparatus of peripheral nerve.

10 distinct clinical symptoms and disruption of paranodal architecture as a pathological correlate.

11 l phenotype and histopathological changes of paranodal architecture of patients with autoantibodies a

12 an important contributor to proper nodal and paranodal architecture.

13 mal myelinated fibres revealed disruption of paranodal architecture.

14 the node of Ranvier where it is required for paranodal axo-glial adhesion.

15 nt galactolipids of myelin exhibit disrupted paranodal axo-glial interactions in the central and peri

16 the galactolipids results in a disruption in paranodal axo-glial interactions, and we show here that

17 fasc155 deficiency), recapitulating impaired paranodal axo-glial junction formation.

18 The formation of paranodal axo-glial junctions is critical for the rapid

19 dependently of its canonical role in forming paranodal axo-glial junctions, as synapse elimination oc

20 asc(NF155)) results in the disruption of the paranodal axo-glial junctions, loss of ion channel segre

21 Jimpy mice do not have intact paranodal axoglial contacts, which is indicated by a com

22 node formation occurs independent of intact paranodal axoglial contacts.

23 supportive role for the partially disrupted paranodal axoglial junction in selectively maintaining N

24 vier) and Nfasc155 (a glial component of the paranodal axoglial junction).

25 antibodies against Caspr, a component of the paranodal axoglial junction, overlaps with these paranod

26 tify additional proteins associated with the paranodal axoglial junction.

27 These include nodes of Ranvier, paranodal axoglial junctions and juxtaparanodes.

28 Paranodal axoglial junctions are critical for maintainin

29 Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier.

30 Paranodal axoglial junctions in myelinated nerve fibers

31 s and adhesion molecules that cluster NF186, paranodal axoglial junctions that function as barriers t

32 ium channels into nodal complexes flanked by paranodal axoglial junctions.

33 red in juxtaparanodal zones, just beyond the paranodal axoglial junctions.

34 ich is directly attributed to the absence of paranodal axoglial junctions.

35 of Caspr at paranodes and destabilization of paranodal axoglial septate junctions (AGSJs) as early as

36 Contactin clusters at the paranodal axolemma during Schwann cell myelination.

37 alities in the molecular organization of the paranodal axolemma.

38 hannels were often improperly located in the paranodal axon membrane, typically associated with impro

39 taparanodal region, directly adjacent to the paranodal axon-glia junctions that flank the nodes of Ra

40 clustering is mediated by the spectrin-based paranodal axonal cytoskeleton.

41 MT pathology and paranodal axonal ovoids were prominent at 6 mo.

42 oss-links neurofilaments, resulting in large paranodal axonal swellings filled with neurofilaments.

43 e of mitochondrial stationary sites in nodal/paranodal axoplasm.

44 aparanodal/internodal axoplasm than in nodal/paranodal axoplasm.

45 nd paranodal barrier, the ECM and CS, or the paranodal barrier and CS all lead to juvenile lethality,

46 oss of axonal betaII spectrin eradicated the paranodal barrier that normally separates juxtaparanodal

47 tly normal nodes, disruptions of the ECM and paranodal barrier, the ECM and CS, or the paranodal barr

48 sed submembranous cytoskeleton comprises the paranodal barriers required for myelinated axon domain o

49 res the coordinated action of internodal and paranodal CAMs.

50 beta, and the Na(+)-channel beta(1) subunit, paranodal caspr and nodal ankyrin(G) was unaltered in 2-

51 ormed nodes of Ranvier which were flanked by paranodal Caspr staining.

52 tochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex.

53 nal knockout mice lacking both NF186 and the paranodal cell adhesion molecule Caspr, demonstrating th

54 directed against both isoforms of the nodal/paranodal cell adhesion molecule neurofascin were identi

55 e destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contac

56 d of the recording period revealed nodal and paranodal changes consistent with acute wallerian degene

57 so show that alphaII spectrin is part of the paranodal complex and that, although not properly target

58 nished Nfasc155 protein levels and prevented paranodal complex formation in neonatal animals.

59 the formation of AGJs because it recruits a paranodal complex implicated in the tethering of glial p

60 al Nfasc155, are components of the nodal and paranodal complexes, respectively.

61 urofascin-null mice have disrupted nodal and paranodal complexes.

62 s, including those that encode the essential paranodal component neurofascin 155 (NF155).

63 al protein betaIV spectrin did not alter the paranodal cytoskeleton.

64 ntification of three novel components of the paranodal cytoskeleton: ankyrinB, alphaII spectrin, and

65 possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune

66 this study suggest that myelin infolding and paranodal damage may represent pathogenic precursors pre

67 th signs of impaired axonal transport and to paranodal defects and abnormal organization of the node

68 i.e., altered neurofilament phosphorylation, paranodal defects, and changes in node of Ranvier number

69 OMgp-null mice failed to reveal any nodal or paranodal defects, or increased nodal collateral sprouti

70 e molecular aberrations underlying nodal and paranodal degenerative changes in type 1 diabetic neurop

71 atrophy, paranodal swelling (P < 0.001), and paranodal demyelination (P < 0.005), without increasing

72 In paranodal demyelination, a gap separates two distinct he

73 ected lysolecithin causes both segmental and paranodal demyelination.

74 e also anticipate the existence of a passive paranodal diffusion barrier at the myelin/noncompact mem

75 Loss of Nfasc186 provokes CNS paranodal disorganization, but this does not contribute

76 Interestingly, the presence of paranodal domains failed to rescue nodal organization in

77 creased in Akt-DD optic nerve, with extended paranodal domains having excess paranodal loops, and the

78 We show that the paranodal domains in MS NAWM are longer on average than

79 elin formation and organization of nodal and paranodal domains in the CNS.

80 oundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitat

81 structural analysis, we demonstrate that the paranodal domains invade the nodal space in Nfasc(NF(1)(

82 e displaced from the juxtaparanodal into the paranodal domains.

83 aberrant actomyosin constriction of axons at paranodal domains.

84 anvier either dissolved or extended into the paranodal domains.

85 r (TNF), IFNgamma, and glutamate can provoke paranodal elongation in cerebellar slice cultures, which

86 Nodal and paranodal expression stabilized in mature myelin, but ov

87 The increase in paranodal frequency with age is 57% in area 17 and 90% i

88 gy of neurologic disorders in which impaired paranodal function contributes to clinical disability.

89 Specialized junctions that form between the paranodal glial membranes and axon flank the nodes and a

90 glia at the nodal gap (i.e., NF186) and the paranodal junction (i.e., Caspr).

91 transverse bands (TBs), the component of the paranodal junction (PNJ) that attaches the myelin sheath

92 out of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction

93 However, the molecular mechanisms underlying paranodal junction assembly are poorly understood.

94 caffolds that facilitate early and efficient paranodal junction assembly in the developing CNS.

95 communication between axons and glia at the paranodal junction can orchestrate the formation of the

96 e internodes in a double strand that flanked paranodal junction components (i.e., Caspr, contactin, a

97 Our results demonstrate that the paranodal junction contains specialized cytoskeletal com

98 Contactin-1-deficiency disrupted paranodal junction formation as evidenced by loss of Cas

99 f myelinated fibres and abnormalities in the paranodal junction morphology.

100 dextran tracers to test the tightness of the paranodal junction of living or fixed myelinated fibers

101 d juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22

102 l Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and t

103 ment), or by axoglial contacts (i.e., at the paranodal junction).

104 dhesion molecule Caspr, demonstrating that a paranodal junction-dependent mechanism can cluster Na(+)

105 Our results reveal that the paranodal junction-dependent mechanism of Na(+)channel c

106 he myelin away from the axon and the forming paranodal junction.

107 ite even without the formation of a distinct paranodal junction.

108 as on the presence of Caspr at the adjacent paranodal junction.

109 mbly of the nodes of Ranvier is found at the paranodal junction.

110 ctrin maintains the diffusion barrier at the paranodal junction.

111 Mouse mutants with paranodal junctional (PNJ) defects display variable degr

112 hat independently of MAG, galactolipids, and paranodal junctional components, immature nodes of Ranvi

113 Examination of the paranodal junctional region of CNS myelinated fibers sho

114 n with the one of the Schwann cells, both at paranodal junctions (with myelin loops) and at nodal gap

115 Paranodal junctions are the largest vertebrate junctiona

116 s achieved, at least in part, by specialized paranodal junctions comprised of the neuronal heterocomp

117 In the absence of NCP1, normal paranodal junctions fail to form, and the organization o

118 The paranodal junctions flank mature nodes of Ranvier and pr

119 Paranodal junctions flank nodes and function as attachme

120 Specialized paranodal junctions form between the axon and the closel

121 ntactin autoantibodies induced alteration of paranodal junctions in myelinated neuronal culture.

122 at is concentrated at central and peripheral paranodal junctions in the adult and during early myelin

123 Paranodal junctions of myelinated nerve fibers are impor

124 ex of Caspr and contactin is targeted to the paranodal junctions via extracellular interactions with

125 es, are highly enriched at the glial side of paranodal junctions where they interact with the essenti

126 ice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K(+) channels.

127 s disrupted in Caspr-null mice with aberrant paranodal junctions, demonstrating that paranodal neuron

128 neurofascin (NF-155), a major constituent of paranodal junctions, has key biochemical characteristics

129 Finally, mutant animals with disrupted paranodal junctions, including those lacking specific my

130 ting to mature nodes, i.e., those flanked by paranodal junctions, requires intracellular interactions

131 ofascin-155 (NF155) enables the formation of paranodal junctions, suggesting that antibody attack aga

132 pr as a major transmembrane component of the paranodal junctions, whose molecular composition has pre

133 dependent accumulation of NF186 requires the paranodal junctions.

134 and require it for development of axon-glial paranodal junctions.

135 155) is required for the assembly of correct paranodal junctions.

136 re does not depend on the presence of mature paranodal junctions.

137 tes but also on specific axoglial contact at paranodal junctions.

138 es and facilitates the efficient assembly of paranodal junctions.

139 esion molecule, is regulated by the flanking paranodal junctions.

140 in, and modestly reduced Caspr clustering at paranodal junctions; it did not significantly affect len

141 n within the internodal periaxonal space and paranodal/juxtaparanodal channels.

142 nodal axoglial junction, overlaps with these paranodal K+ channels.

143 ions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is in

144 of the infarct diameter away, both nodal and paranodal length increase by approximately 20% and 80%,

145 because in area 17 the 11% increase in mean paranodal length with age is insufficient to account for

146 e beyond the nodal area and the formation of paranodal-like junctions at the nodal gap.

147 oss-linking, stabilization, and formation of paranodal lipid raft assemblies.

148 Furthermore, we show that the paranodal localization of ankyrinB is disrupted in Caspr

149 , and exhibit progressive disruption of axon-paranodal loop interactions in the CNS.

150 Consequently, these mice displayed paranodal loops either above or underneath compact myeli

151 of myelinated axons with thick sheaths, some paranodal loops fail to contact the axolemma.

152 ns fail to form, and the organization of the paranodal loops is disrupted.

153 e matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier.

154 tor type 2 (FGFR2) is highly enriched at the paranodal loops of myelin.

155 ke junctions that form between axons and the paranodal loops of myelinating cells.

156 orm between the axon and the closely apposed paranodal loops of myelinating glia.

157 e findings indicate that interactions of the paranodal loops with the axon promote the transition in

158 ith extended paranodal domains having excess paranodal loops, and the density of nodes of Ranvier was

159 k the node of Ranvier and in overlying glial paranodal loops, proteins are arranged within circumscri

160 within an expanded lysosomal compartment of paranodal loops.

161 to the formation of a set of closely apposed paranodal loops.

162 Similarly, immunolabeling for the paranodal marker caspr reveals irregular caspr-labeled p

163 rohibits protein diffusion out of contiguous paranodal membranes.

164 berrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1,

165 Both pathways are affected in the paranodal mutants.

166 Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine)

167 sides of the nodal membrane, displacing the paranodal myelin and widening the nodal gap.

168 nd sciatic nerves correctly localized at the paranodal myelin areas.

169 ession of Caspr and leaves NF155 on apposing paranodal myelin disengaged.

170 Acute disruption of paranodal myelin dramatically increases stimulation-indu

171 ocal myelin thickening, abnormalities of the paranodal myelin loops, and focal absence of paranodal s

172 ophy of myelinated PNS axons that results in paranodal myelin tomaculi and axonal degeneration.

173 rant paranodal junctions, demonstrating that paranodal neuron-glia interactions regulate the organiza

174 cted to the nodal gap and is absent from the paranodal or juxtaparanodal region.

175 alities including myelin outfolds, disrupted paranodal organization, and ectopic ensheathment of neur

176 Paranodal pathology was investigated by immunofluorescen

177 uce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and c

178 nt to account for an age-related increase in paranodal profile frequency.

179 marker caspr reveals irregular caspr-labeled paranodal profiles, suggesting that there may be age-rel

180 Three sites were examined: paranodal prospective neural plate ectoderm, containing

181 athies for antibodies directed against nodal/paranodal protein antigens using a live cell-based assay

182 occurred normally in mice lacking the axonal paranodal protein Caspr.

183 We determined myelin status by examining paranodal protein distribution on anterogradely labeled,

184 hannels were used to identify internodes and paranodal protein distribution properties were used as a

185 odin/contactin-associated protein (Caspr), a paranodal protein that is a potential neuronal mediator

186 Neurofascin 155 high is a myelin paranodal protein while the distribution of neurofascin

187 Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated pr

188 ensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate det

189 and glial membranes highly enriched in these paranodal proteins and then used mass spectrometry to id

190 etic ablation of genes encoding the critical paranodal proteins Caspr, contactin (Cont), and the myel

191 Autoantibodies against paranodal proteins have been described in patients with

192 y (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1),

193 Immunofluorescence-labelling of paranodal proteins of dermal myelinated fibres revealed

194 Linkage of paranodal proteins to the underlying cytoskeleton likely

195 by immunoglobulin G4 antibodies to nodal or paranodal proteins, and could require alternative treatm

196 nctions have emerged, which suggest that the paranodal region may act as an ionic barrier and a molec

197 membranes likely correspond to the nodal and paranodal region of the axon-Schwann cell unit.

198 se vertebrate junctions are localized to the paranodal region of the nodes of Ranvier, between axons

199 e found to have morphological defects in the paranodal region, exhibiting increased nodal length as c

200 myelin loops that protrude into the axons at paranodal regions and near Schmidt-Lanterman incisures o

201 -myelin binding, was not concentrated in the paranodal regions but was diffusely distributed along th

202 these were broad, and all were excluded from paranodal regions of axoglial contact.

203 majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap t

204 er, these same complexes are also present in paranodal regions of some spinal cord axons, and stainin

205 e and becomes strikingly concentrated in the paranodal regions of the axon, suggesting that it redist

206 isrupted and ultrastructural analysis showed paranodal regions that were completely devoid of AGSJs,

207 nclude the nodes of Ranvier and the flanking paranodal regions where glial cells closely appose and f

208 ntibody-mediated disease affecting the nodal/paranodal regions.

209 Ultrastructural analysis of paranodal segments from optic nerve of aged monkeys show

210 gth of node of Ranvier segments and adjacent paranodal segments.

211 In addition, new roles for axo-glial paranodal septate junctions have emerged, which suggest

212 The mutant mice lack paranodal septate junctions, resulting in the diffusion

213 inked contactin enables the formation of the paranodal septate-like axo-glial junctions in myelinated

214 paranodal myelin loops, and focal absence of paranodal septate-like junctions between the terminal lo

215 At the ultrastructural level, the paranodal septate-like junctions immediately adjacent to

216 al glial cell adhesion molecule expressed in paranodal septate-like junctions of peripheral and centr

217 opic analysis of the junctions showed intact paranodal septate-like junctions.

218 ertebrate SJ is homologous to the vertebrate paranodal SJ.

219 ntactin, and Neuroglian are expressed at the paranodal SJs and play a key role in axon-glial interact

220 ies also induced the loss of Nfasc155 and of paranodal specialization and resulted in conduction alte

221 oltage-gated Na(+) channel clusters but lack paranodal specializations, axonal mitochondrial motility

222 equires oligodendrocyte-axon interactions at paranodal specializations.

223 Thus, the paranodal spectrin-based submembranous cytoskeleton comp

224 ng that neurofascin 155 high is required for paranodal stability.

225 , indicating that complete disruption of the paranodal structure and movement of Kv1.2 channels prece

226 f transverse bands, which serve to stabilize paranodal structure over time as well as the organizatio

227 urofascin 155 low is incapable of preserving paranodal structure, thus indicating that neurofascin 15

228 erized by a progressive deterioration of the paranodal structure.

229 ing that there may be age-related changes in paranodal structure.

230 ern the formation and maintenance of overall paranodal structure.

231 ated that oligodendrocytes were present, and paranodal structures formed, as early as postnatal day 7

232 A significant early alteration in Nfasc155+ paranodal structures occurs within and adjacent to activ

233 ongly against hippocampal neurons (8.6%) and paranodal structures on peripheral nerve.

234 diet resulted in significant axonal atrophy, paranodal swelling (P < 0.001), and paranodal demyelinat

235 ugh an elongated helical pathway between the paranodal terminal loops of the myelin sheath.

236 uirements controlling the association of the paranodal tripartite complex in vivo.

237 on resulted in redistribution of ADAM22 into paranodal zones.