ライフサイエンスコーパス: spectrin

1 tations in the cytoskeletal protein beta-III-spectrin.

2 those enriched in nodal ankyrinG and betaIV spectrin.

3 consist of diverse beta subunits and alphaII spectrin.

4 Sptan1(f/f) mice for deletion of CNS alphaII spectrin.

5 es at the ankyrin- and actin-binding ends of spectrin.

6 S) composed of actin rings interconnected by spectrin.

7 mational change and for recruitment of beta4-spectrin.

8 rength of the association between lipids and spectrin.

9 ctrin causes profound reductions in all beta spectrins.

10 tiple isoforms of Nesprin1 (nuclear envelope spectrin 1) that associate with the nuclear envelope (NE

11 form a unique membrane skeleton, composed of spectrin, 4.1R-complex, and ankyrinR-complex components,

12 l and in vitro models have revealed beta-III spectrin, a cytoskeletal protein present throughout the

13 Depletion of betaII-spectrin, a key component of the MPS, suppresses retrogr

14 ectromotility, we focused on the betaV giant spectrin, a major component of the outer hair cells' cor

15 the interaction between the mutant beta-III-spectrin ABD and actin in live cells.

16 A beta-III-spectrin ABD mutation (L253P) linked to spinocerebellar

17 In addition, we observed that spectrin, actin, and adducin also form a 2D polygonal la

18 we investigated the spatial organizations of spectrin, actin, and adducin, an actin-capping protein,

19 ne skeleton is a pseudohexagonal meshwork of spectrin, actin, protein 4.1R, ankyrin, and actin-associ

20 inding by SCA5 beta-spectrin interferes with spectrin-actin cytoskeleton dynamics, leading to a loss

21 protein that links membrane proteins to the spectrin-actin cytoskeleton, associates with VE-cadherin

22 he dissociation of L1 from ankyrin-G and the spectrin-actin cytoskeleton.

23 ing and bundling protein associated with the spectrin-actin junctions of mature erythrocytes.

24 embly and offer additional insights into the spectrin-actin-4.1R-based membrane skeleton as an emergi

25 eading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane

26 Exon 16 of protein 4.1R encodes a spectrin/actin-binding peptide critical for erythrocyte

27 vels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLK

28 depolymerization resistant and sensitive to spectrin, adducin, and nucleator deficiency, consistent

29 used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and

30 Spectrin aggregate formation in fibroblasts with mutatio

31 tion compared to mice lacking beta1 or beta4 spectrin alone, including profound disruption of AIS Na(

32 ed cytoskeletal proteins, including beta-III-spectrin, alpha-actinin, filamin, and dystrophin.

33 horylated forms of its substrates IRSp53 and spectrin alphaII.

34 biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells

35 However, because spectrins also participate in assembly of axon initial s

36 Actin binding proteins, including spectrin and alpha-actinin, serve as molecular linkages

37 in cKO hearts exhibited remodeling of alphaI spectrin and altered beta-spectrin expression and locali

38 e transport, while double knockout of betaII-spectrin and AnkB nearly eliminated transport.

39 om nodes and axon initial segments of betaIV-spectrin and AnkG mutant mice.

40 beta-spectrin dominantly mislocalizes alpha-spectrin and ankyrin-2, components of the endogenous spe

41 a network of actin filaments cross-linked by spectrin and attached to membrane proteins.

42 As previously described, we show that alpha-Spectrin and beta-Spectrin are essential to maintain a m

43 ectrins, where beta4 spectrin is the primary spectrin and beta1 spectrin can substitute; each is suff

44 e1, we identify unique contributions for the spectrin and carboxy-terminal domains during different p

45 Functional studies show that the spectrin and GEFD1 variants cause a TRIO-mediated hyper-

46 iction-independent cell elongation, as alpha-Spectrin and integrin mutant cells fail to columnarize.

47 Our results identify alpha-Spectrin and integrins as novel regulators of apical con

48 that IQCJ-SCHIP1 also interacts with betaIV-spectrin and Kv7.2/3 channels and self-associates, sugge

49 In contrast, in areas where spectrin and lipids are not associated, spectrin modifie

50 We conclude that the spectrin and microtubule cytoskeletons work in combinati

51 Through recruiting beta(Heavy)-Spectrin and MyosinV to the apical membrane, Crumbs main

52 g the structure of spectrin in situ, the way spectrin and other proteins bind to actin, how the membr

53 dification of the cytoskeletal proteins beta-spectrin and PIEZO1.

54 oils and plectonemes in the sensory axons of spectrin and tau double mutants.

55 ical stress and propose that defects in beta-spectrin and tau may sensitize neurons to damage.

56 elements enriched in Protein 4.1B and betaII spectrin and those enriched in nodal ankyrinG and betaIV

57 of both orientations and natural lengths of spectrin and updated copy numbers of proteins.

58 Spectrins and actin form a periodic cytoskeleton propose

59 bind them assemble combinations of ankyrins, spectrins and other cytoskeletal scaffolding proteins, w

60 cently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like s

61 Actin, spectrin, and associated molecules form a membrane-assoc

62 Actin, spectrin, and associated molecules form a periodic, subm

63 ls rescues junctional localization of actin, spectrin, and E-cadherin assembly at the AJs.

64 hed light on the mechanism by which beta-III-spectrin, and likely similar actin-binding proteins, int

65 mportant for the efficient assembly of alpha-spectrin, and may reduce its dependence on chaperones.

66 equired for binding and recruitment of beta4-spectrin, and normally occurs early in development of th

67 Actin, spectrin, and related molecules form a membrane-associat

68 GFAP, Iba1, alphaII-spectrin, and SBDP remained unchanged.

69 precursor protein (APP), GFAP, Iba1, alphaII-spectrin, and spectrin breakdown products (SBDP).

70 ity of three protein model systems: barnase, spectrin, and T4 lysozyme.

71 Cytoskeletal proteins of the axon (betaIV spectrin, ankyrin G) exhibit a high degree of one-dimens

72 otably, mutations of SPTNB2 encoding betaIII spectrin are associated with neurodegenerative syndromes

73 cribed, we show that alpha-Spectrin and beta-Spectrin are essential to maintain a monolayered FE, but

74 ein 4.1B and the cytoskeleton protein betaII spectrin are mislocalized in the axon, and assembly of t

75 We also show that ankyrin R and betaI spectrin are not sufficient to prevent nodal disorganiza

76 Spectrins are cytoskeletal proteins essential for membra

77 olayered FE, but, contrary to previous work, spectrins are not required to control proliferation.

78 Thus, nodal spectrins are required to maintain nodal Na(+) channel c

79 CA type-5 whereas homozygous mutations cause spectrin associated autosomal recessive ataxia type-1 (S

80 yndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxi

81 ggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxi

82 of spinocerebellar ataxia type-5 (SCA5) and spectrin-associated autosomal recessive cerebellar ataxi

83 end protein Patronin, a calmodulin-regulated spectrin-associated protein (CAMSAP) homologue, which fu

84 MT minus-end regulator calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), Camsap3 (tm1a/t

85 We found that betaII-spectrin associates with KIF3A, KIF5B, KIF1A, and dynact

86 periodic cytoskeleton with betaIV and betaII spectrin at nodes of Ranvier and paranodes, respectively

87 constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid b

88 of the band 3-ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane.

89 The spectrin-based membrane skeleton maintains the biconcave

90 e thin filaments of striated muscles and the spectrin-based membrane skeleton, use barbed and pointed

91 ical coupling between IgCAMs and the lateral spectrin-based membrane skeleton.

92 red cell membrane skeleton is the model for spectrin-based membrane skeletons in all cells, and beca

93 re, we investigate the behavior of the actin-spectrin-based Membrane-associated Periodic Skeleton (MP

94 xon stability through establishing the actin-spectrin-based membrane-associated periodic skeleton as

95 f Na(+)channel clustering is mediated by the spectrin-based paranodal axonal cytoskeleton.

96 exhibited reduced axon growth, loss of actin-spectrin-based periodic membrane skeleton, and impaired

97 ARCA1) are mirrored in mice lacking beta-III spectrin (beta-III-/-).

98 nic inflammation in wild-type (WT) and beta2-spectrin (beta2SP)(+/-) (SPTBN1) mice.

99 Epigenetic silencing of beta2-spectrin (beta2SP, encoded by SPTBN1), a SMAD adaptor fo

100 In frog hair cells, spectrin betaV was invariably detected near the apical j

101 aptive evolution at multiple sites along the spectrin-betaV amino acid sequence in the lineage leadin

102 For instance, in areas where spectrin binds to the lipid bilayer, spectrin filaments

103 L1, S100 calcium binding protein B, alpha-II-spectrin breakdown product 150, interleukin 6, interleuk

104 ein (APP), GFAP, Iba1, alphaII-spectrin, and spectrin breakdown products (SBDP).

105 teolytic neuronal injury biomarkers (alphaII-spectrin breakdown products, SBDPs) and glial cell injur

106 4 spectrin is the primary spectrin and beta1 spectrin can substitute; each is sufficient for proper n

107 At paranodes, both axonal proteins (betaII spectrin, Caspr) and glial proteins (neurofascin-155, an

108 n the actin-binding domain (ABD) of beta-III-spectrin causes high-affinity actin binding and decrease

109 Whereas loss of beta4 spectrin causes motor impairment and disrupts AIS, loss

110 of both sexes and found that loss of alphaII spectrin causes profound reductions in all beta spectrin

111 nhances and decreases multilayering of alpha-Spectrin cells, respectively.

112 obal cardiac spectrin regulation, as alphaII spectrin cKO hearts exhibited remodeling of alphaI spect

113 alphaII spectrin cKO mice displayed significant structural, cell

114 ion volume, enhanced calpain-induced alphaII-spectrin cleavage, and increased cell death in perilesio

115 f L1CAM by the cytoskeletal ankyrin-G/betaIV-spectrin complex.

116 Using a new alphaII spectrin conditional knock-out mouse, we show that alpha

117 keletal proteins ankyrin-G (AnkG) and betaIV-spectrin control the organization of these complexes and

118 Previously, we showed that a hierarchy of spectrin cytoskeletal proteins maintains nodal Na(+) cha

119 on-glia interactions converge on ankyrin and spectrin cytoskeletal proteins to cluster nodal Na(+) ch

120 se results demonstrate the importance of the spectrin cytoskeleton both at the AIS and throughout the

121 imal model has tested the requirement of the spectrin cytoskeleton in maintenance of axon integrity.

122 uries and diseases because disruption of the spectrin cytoskeleton is a common molecular pathology.

123 iption of the entropic elasticity of the RBC spectrin cytoskeleton, including domain unfolding/refold

124 dimensions of the "corrals" of the cortical spectrin cytoskeleton.

125 and ankyrin-2, components of the endogenous spectrin cytoskeleton.

126 t within the protein network of the cortical spectrin cytoskeleton.

127 Neuronal spectrin cytoskeletons consist of diverse beta subunits

128 s problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated

129 results demonstrate the broad importance of spectrin cytoskeletons for nervous system function and d

130 ut the nervous system.SIGNIFICANCE STATEMENT Spectrin cytoskeletons play diverse roles in neurons, in

131 betaII-spectrin deficiency caused severe defects in long-range

132 At the cellular level, alphaII spectrin deficiency resulted in altered expression, targ

133 activates nonsense mediated decay leading to spectrin deficiency.

134 use model of cardiomyocyte-selective alphaII spectrin-deficiency (cKO) and used this model to define

135 alphaII spectrin-deficient mice die before 1 month of age and ha

136 We analyzed alphaII spectrin-deficient mice of both sexes and found that los

137 We analyzed alphaII spectrin-deficient mice of both sexes and found that, in

138 on integrity, we generated mice with alphaII spectrin-deficient peripheral sensory neurons.

139 In the absence of betaIII spectrin, dendritic spines collapse onto dendrites.

140 We demonstrate the role of the periodic spectrin-dependent cytoskeleton in axons and show that l

141 ed by large-diameter axons, and that alphaII spectrin-dependent cytoskeletons are also required for a

142 apses, the presynaptic structures in betaIII spectrin-depleted neurons make shaft synapses that exhib

143 odes, respectively, but that loss of alphaII spectrin disrupts this organization.

144 ic flexibility of PRC1, suggests that the MT-spectrin domain interface determines the geometry of the

145 Residues in the spectrin domain of PRC1 contacting the MT are highly con

146 Interestingly, the angle of the spectrin domain on the MT surface corresponds to the pre

147 rant dependence of the unfolded state of the spectrin domain R17 and the intrinsically disordered pro

148 We show that the spectrin domain uses conserved basic residues to promote

149 ) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein inv

150 We show that SCA5 beta-spectrin dominantly mislocalizes alpha-spectrin and anky

151 We have studied the role of spectrins during epithelia morphogenesis using the Droso

152 one of two alpha spectrin genes and alphaII spectrin dysfunction is linked to alterations in axon in

153 modeling of alphaI spectrin and altered beta-spectrin expression and localization.

154 s diffusion barrier based on 4.1B and betaII spectrin expression in Caspr-null mice.

155 s the generally expressed member of the beta-spectrin family of elongated polypeptides that form micr

156 reduced compared to the thermal motion when spectrin filaments are held at equilibrium.

157 It also predicts that because the spectrin filaments are under entropic tension, the therm

158 Lastly, our model predicts that because spectrin filaments are under tension, any axonal injurie

159 We also showed that spectrin filaments could modify transverse diffusion of

160 ured as a series of actin rings connected by spectrin filaments that are held under tension.

161 he membrane skeleton due to the inability of spectrin filaments to spontaneously form their initial u

162 r tension, any axonal injuries that lacerate spectrin filaments will likely lead to a permanent disru

163 s where spectrin binds to the lipid bilayer, spectrin filaments would restrict diffusion of proteins

164 ures that corroborate proposed mechanisms of spectrin flexibility and elasticity.

165 n over 10 months, primarily affecting betaIV spectrin, followed by NaV channels, with modest impact o

166 r define the important role of AIS and nodal spectrins for nervous system function.

167 Spectrins form a submembranous cytoskeleton proposed to

168 Electron microscopy revealed that betaIII spectrin forms a detergent-resistant cytoskeletal networ

169 and found that, in myelinated axons, alphaII spectrin forms a periodic cytoskeleton with betaIV and b

170 erminal hydrolase L1, 2.5-fold increase; AII spectrin fragments, 1.9-fold increase; claudin-5, 2.7-fo

171 leton in axons and show that loss of alphaII spectrin from PNS axons causes preferential degeneration

172 Loss-of beta-III spectrin function appears to underpin cerebellar dysfunc

173 thogenesis mediated through loss of beta-III spectrin function by studying EAAT4 and GLAST knockout m

174 pectrin heterodimer formation and/or alphaII spectrin function.

175 1, but molecular mechanisms linking betaIII spectrin functions to neuronal pathologies remain unreso

176 lphaII spectrin (SPTAN1) is one of two alpha spectrin genes and alphaII spectrin dysfunction is linke

177 axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mech

178 r impairment and disrupts AIS, loss of beta1 spectrin has no discernable effect on central nervous sy

179 Remarkably, mice lacking nodal beta spectrins have normal nodal Na(+) channel clustering dur

180 1 gene, encoding the non-erythrocyte alphaII spectrin, have been associated with severe West syndrome

181 Our results suggest that nodal alphaII spectrin helps resist the mechanical forces experienced

182 3 patients with mutations located within the spectrin heterodimer contact site exhibited severe and p

183 e alpha20 repeat is important for alpha/beta spectrin heterodimer formation and/or alphaII spectrin f

184 ing in the nucleation site of the alpha/beta spectrin heterodimer region.

185 harbouring mutations outside the alpha/beta spectrin heterodimerization domain, four had normal brai

186 bryonic lethal, the in vivo roles of alphaII spectrin in adult heart are unknown and untested.

187 ed this model to define the roles of alphaII spectrin in cardiac function.

188 We show that betaIII spectrin in hippocampal and cortical neurons from rodent

189 ers the mobility and recruitment of beta-III-spectrin in mammalian cells, pointing to a potential dis

190 II-spectrin in neurons by knockout of betaII-spectrin in mouse neural progenitors.

191 We addressed in vivo functions of betaII-spectrin in neurons by knockout of betaII-spectrin in mo

192 luding questions concerning the structure of spectrin in situ, the way spectrin and other proteins bi

193 Here, we report an essential role for spectrin in specifying cell shape by transmitting intrac

194 o animal model to study the roles of alphaII spectrin in the cardiomyocyte.

195 F3A, KIF5B, KIF1A, and dynactin, implicating spectrin in the coupling of motors and synaptic cargo.

196 alphaII/betaII aggregates and alphaII spectrin in the insoluble protein fraction were observed

197 ilure we tested the in vivo roles of alphaII spectrin in the vertebrate heart.

198 Here, we generated mice lacking nodal spectrins in peripheral sensory neurons to uncouple thei

199 To determine the role of spectrins in the nervous system, we generated Sptan1(f/f

200 mong axons, but the density of nodal alphaII spectrin increases with axon diameter.

201 that the interaction of alpha-synuclein with spectrin initiates pathological alteration of the actin

202 In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequa

203 microscopy, we show that alphaII and betaIV spectrin interact and form a periodic AIS cytoskeleton.

204 hat high-affinity actin binding by SCA5 beta-spectrin interferes with spectrin-actin cytoskeleton dyn

205 Finally, we found that spectrin is capable of adopting a similar periodic organ

206 We show that the density of nodal betaIV spectrin is constant among axons, but the density of nod

207 n which an equivalent mutant Drosophila beta-spectrin is expressed in neurons that extend complex den

208 We show that nodal alphaII spectrin is found at greater densities in large-diameter

209 Although alphaII spectrin is found in neurons in both axonal and somatode

210 Thus, betaIII spectrin is necessary for formation of the constricted s

211 tional knock-out mouse, we show that alphaII spectrin is required for AIS assembly, neuronal excitabi

212 Mechanistically, we show that spectrin is required for tethering cortical F-actin to c

213 betaII-spectrin is the generally expressed member of the beta-s

214 a hierarchy of nodal spectrins, where beta4 spectrin is the primary spectrin and beta1 spectrin can

215 One function of beta-III spectrin is the stabilization of the Purkinje cell-speci

216 Loss of nodal spectrins is accompanied by an axon injury response and

217 (AnkR), compensates for loss of nodal beta4 spectrin, it cannot compensate at AIS.

218 ynaptic terminals is not affected by betaIII spectrin knockdown.

219 As global alphaII spectrin knockout mice are embryonic lethal, the in vivo

220 a indicate that the mechanical properties of spectrin-like repeats in utrophin are more in line with

221 arborization coincident with decreased beta-spectrin localization in distal dendrites.

222 oltage-gated sodium (NaV) channel and betaIV spectrin loss with reduced effects on neurofascin 186.

223 Furthermore, human alphaII spectrin loss-of-function variants cause neurological di

224 dic Skeleton (MPS), and effects of actin and spectrin manipulations in sensory axon degeneration.

225 eals that restructuring and constraining the spectrin meshwork can fully account for the observed cha

226 here spectrin and lipids are not associated, spectrin modifies the diffusion of TMPs and IMPs of the

227 estigated the mechanical unfolding of single spectrin molecules over a broad range of loading rates a

228 plice acceptor site, perturbing normal alpha-spectrin mRNA splicing and creating an elongated mRNA tr

229 Furthermore, spectrin mutant cells show differentiation and polarity

230 constriction, and Yki-mediated hyperplasia, spectrin mutant cells, despite showing myosin II activat

231 of nodes similar to that observed in betaIV-spectrin mutant mice, revealing that IQCJ-SCHIP1 contrib

232 thology of human syndromes caused by betaIII spectrin mutations.

233 However, in many hematological disorders the spectrin network and lipid bilayer of diseased RBCs may

234 odel and predict the extent to which dynamic spectrin network connectivity can protect against failur

235 gher organizational level of the AnkG/betaIV-spectrin network critical for node integrity.

236 of density and microscopic structure of its spectrin network from proteomics and cryo-electron tomog

237 also defines a new picture of a much denser spectrin network than assumed in prior studies.

238 By applying finite deformation to the spectrin network, we obtain the total free energy and st

239 hrough its interactions with the AnkG/betaIV-spectrin network.

240 onnection between the molecular structure of spectrin networks and constitutive laws and also defines

241 betaII-spectrin-null neurons exhibited reduced axon growth, los

242 in rather than those reported for repeats in spectrin or dystrophin.

243 ompound libraries for modulators of beta-III-spectrin, or disease-linked spectrin-related proteins, f

244 Knockout of ankyrin-B (AnkB), a betaII-spectrin partner, primarily impaired retrograde organell

245 Here, we show that alphaII spectrin partners with betaIV spectrin to form a periodi

246 We show that a cytoskeletal protein betaIII spectrin plays a key role for the formation of narrow sp

247 molecular level, we demonstrate that alphaII spectrin plays a nodal role for global cardiac spectrin

248 onse of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in

249 Thus, betaII-spectrin promotes both axon growth and axon stability th

250 pected roles for the multifunctional alphaII spectrin protein in the heart.

251 stress, exploiting mutations in UNC-70 beta-spectrin, PTL-1 tau/MAP2-like and MEC-7 beta-tubulin pro

252 Here, we show that betaH-spectrin regulates the placement of intermediate filamen

253 , based on pronounced alterations in alphaII spectrin regulation in human heart failure we tested the

254 ectrin plays a nodal role for global cardiac spectrin regulation, as alphaII spectrin cKO hearts exhi

255 tors of beta-III-spectrin, or disease-linked spectrin-related proteins, for therapeutic development.

256 ons the mechanical unfolding of dystrophin's spectrin repeat 1 and related the changes in the protein

257 ots in the TRIO sequence, one in the seventh spectrin repeat and one in the RAC1-activating GEFD1.

258 isorders clustering in the GEFD1 and seventh spectrin repeat domains and highlights the importance of

259 als with a pathogenic variant in the seventh spectrin repeat have a more severe ID associated with ma

260 mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous

261 tion of desmin (or nesprin [nuclear envelope spectrin repeat protein]-3, its binding partner in the L

262 Nesprins are highly conserved spectrin repeat-containing scaffold proteins predominant

263 Nesprins, nuclear envelope spectrin-repeat proteins encoded by the SYNE1 and SYNE2

264 contain a plakin domain formed by up to nine spectrin repeats (SR1-SR9) and an SH3 domain.

265 ree different subdomains of desmoplakin: two spectrin repeats and a Src homology 3 domain.

266 of Rac GTPase: Abl gates the activity of the spectrin repeats of Trio, allowing them to relieve intra

267 edly different unfolding characteristics for spectrin repeats within the N-terminal actin-binding hal

268 proteins to the nuclear envelope through its spectrin repeats, acting as an adaptor between nesprin-1

269 itin immunoglobulin domain and alpha-actinin spectrin repeats.

270 and/or C-helices within each of the mutated spectrin repeats.

271 betaII-spectrin required phosphoinositide lipid binding to prom

272 n of gAnkG that prevent recruitment of beta4-spectrin, resulting in a lower density and more elongate

273 Knockdown of betaIII spectrin results in a significant decrease in the densit

274 ecently discovered membrane-associated actin-spectrin scaffold plays a prominent mechanical role.

275 methods on a microcrystalline protein (alpha-spectrin SH3 domain), for which we are able to identify

276 , mice lacking both neuronal beta1 and beta4 spectrin show exacerbated nervous system dysfunction com

277 a theoretical model, we argue that the actin-spectrin skeleton acts as an axonal tension buffer by re

278 this pathway, thereby identifying the alpha-spectrin SPC-1.

279 IQCJ-SCHIP1 binding requires a betaIV-spectrin-specific domain and Kv7 channel 1-5-10 calmodul

280 rous mutations in erythrocyte membrane alpha-spectrin (SPTA1).

281 alphaII spectrin (SPTAN1) is one of two alpha spectrin genes and

282 gous mutations in the gene encoding beta-III spectrin (SPTBN2) underlie SCA type-5 whereas homozygous

283 drites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell pr

284 lied to the analysis of a model protein of a spectrin tandem repeat that exemplified an intuitive sta

285 al complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given

286 The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilaye

287 y reversibly unfolding repeat domains of the spectrin tetramers to release excess mechanical stress.

288 e actin filaments connected to each other by spectrin tetramers, and the lipid bilayer, which is teth

289 are periodically spaced along the neurite by spectrin tetramers, forming a quasi-1D lattice structure

290 Thus, in the absence of spectrin, the weakened attachment of cortical F-actin to

291 s scaffold of interactions connects beta-III spectrin to a wide variety of proteins implicated in the

292 w that alphaII spectrin partners with betaIV spectrin to form a periodic cytoskeleton at the AIS.

293 sures ordered recruitment of gAnkG and beta4-spectrin to the AIS.

294 ional actin and attenuate the recruitment of spectrin to the AJs and also reduce E-cadherin during th

295 Although beta1 spectrin, together with AnkyrinR (AnkR), compensates for

296 domains from the cytoskeletal protein alpha-spectrin using force profile analysis (FPA).

297 ng mice lacking beta1, beta4, or beta1/beta4 spectrins, we show this hierarchy does not function at a

298 We demonstrate a hierarchy of nodal spectrins, where beta4 spectrin is the primary spectrin

299 nodal Na(+) channels requires axonal betaII spectrin which is concentrated at paranodes.

300 that results from aberrant splicing of alpha-spectrin, which in turn leads to abnormal erythrocyte me