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

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

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

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

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

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

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

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

11 mal myelinated fibres revealed disruption of paranodal architecture.

12 an important contributor to proper nodal and paranodal architecture.

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

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

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

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

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

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

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

20 node formation occurs independent of intact paranodal axoglial contacts.

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

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

23 tify additional proteins associated with the paranodal axoglial junction.

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

25 Paranodal axoglial junctions are critical for maintainin

26 Paranodal axoglial junctions in myelinated nerve fibers

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

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

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

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

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

32 alities in the molecular organization of the paranodal axolemma.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

60 In paranodal demyelination, a gap separates two distinct he

61 ected lysolecithin causes both segmental and paranodal demyelination.

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

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

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

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

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

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

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

69 e displaced from the juxtaparanodal into the paranodal domains.

70 anvier either dissolved or extended into the paranodal domains.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

91 ctrin maintains the diffusion barrier at the paranodal junction.

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

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

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

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

96 Paranodal junctions are the largest vertebrate junctiona

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

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

99 Paranodal junctions flank nodes and function as attachme

100 Specialized paranodal junctions form between the axon and the closel

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

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

103 Paranodal junctions of myelinated nerve fibers are impor

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

136 within an expanded lysosomal compartment of paranodal loops.

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

138 rohibits protein diffusion out of contiguous paranodal membranes.

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

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

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

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

143 Acute disruption of paranodal myelin dramatically increases stimulation-indu

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

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

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

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

148 Paranodal pathology was investigated by immunofluorescen

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

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

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

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

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

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

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

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

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

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

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

160 Autoantibodies against paranodal proteins have been described in patients with

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

183 ertebrate SJ is homologous to the vertebrate paranodal SJ.

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

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

186 equires oligodendrocyte-axon interactions at paranodal specializations.

187 Thus, the paranodal spectrin-based submembranous cytoskeleton comp

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

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

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

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

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

193 ern the formation and maintenance of overall paranodal structure.

194 erized by a progressive deterioration of the paranodal structure.

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

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

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

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

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

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

201 on resulted in redistribution of ADAM22 into paranodal zones.