ライフサイエンスコーパス: thin filament

1 wo myosin heads are required to activate the thin filament.

2 y of cNTnC within the context of the cardiac thin filament.

3 e azimuthal motion of tropomyosin around the thin filament.

4 ve cardiac myosin-binding protein C with the thin filament.

5 is thought to be a disease of the sarcomere thin filament.

6 form cross-bridges with the actin-containing thin filament.

7 neighboring molecules 400 nm along the actin thin filament.

8 T45-74, attenuated maximal activation of the thin filament.

9 n gene encodes a component of the sarcomeric thin filament.

10 ng the whole approximately 1 mum length of a thin filament.

11 2+) binding to Tn with myosin binding to the thin filament.

12 ust rapidly attach and detach from the actin thin filament.

13 nI) functions as the molecular switch of the thin filament.

14 creased the Ca(2+) sensitivity of TnC on the thin filament.

15 e cooperativity of calcium activation of the thin filament.

16 of the C-domain of cTnI in the reconstituted thin filament.

17 nfluence calcium-dependent activation of the thin filament.

18 es involving the constituent proteins of the thin filament.

19 t mutations in all components of the cardiac thin filament.

20 olve different conformational changes in the thin filament.

21 that are associated with the skeletal muscle thin filament.

22 el, calcium modulates myosin's access to the thin filament.

23 d to laterally activate a regulatory unit of thin filament.

24 ssumes a single myosin head can activate the thin filament.

25 esulted in shortening and disorganization of thin filaments.

26 ned by an interaction between MyBP-C and the thin filaments.

27 n, showing that C1mC2 directly activates the thin filaments.

28 ted by an interaction between MyBP-C and the thin filaments.

29 l effects of N-terminal fragments binding to thin filaments.

30 the thick filaments and on troponin C in the thin filaments.

31 for tuning the Ca(2+) regulation of cardiac thin filaments.

32 s were proposed to maintain the integrity of thin filaments.

33 nt biochemical model system of reconstituted thin filaments.

34 s to facilitate the breakdown of Z-bands and thin filaments.

35 reduced fiber atrophy and the rapid loss of thin filaments.

36 and myosin cross-bridge (XB) formation along thin filaments.

37 from the thick filament backbone toward the thin filaments.

38 than myosin cross-bridges between thick and thin filaments.

39 nd double-hexagonal arrangement of thick and thin filaments.

40 protein localized at the pointed end of the thin filaments.

41 mere length relations, indicative of shorter thin filaments.

42 uted WT and cardiac troponin T R92L and R92W thin filaments.

43 r potential interactions with both thick and thin filaments.

44 ed increased mass/ordering in both thick and thin filaments.

45 nding stiffness of F-actin and reconstructed thin filaments.

46 le the N-terminus extends toward neighboring thin filaments.

47 an increase in the bending stiffness of the thin filaments.

48 olecules of myosin binding to and activating thin filaments.

49 fragment 1: evidence for three states of the thin filament."

50 number of different molecules, including the thin-filament accessory proteins tropomyosin and troponi

51 ther ubiquitin ligase, Trim32, ubiquitylates thin filament (actin, tropomyosin, troponins) and Z-band

52 (K206I), we tested the Ca(2+) dependence of thin filament-activated myosin-S1-ATPase activity in a r

53 known about how it modulates the kinetics of thin filament activation and myofibril relaxation as Ca(

54 mutations (S23D/S24D-cTnI), directly affects thin filament activation and myofilament relaxation kine

55 n, via PKA phosphorylation of cTnI, may slow thin filament activation and result in increased myofila

56 ition, and that this movement corresponds to thin filament activation in the motility assay.

57 signal by the cardiac sarcomere to modulate thin filament activation levels occurs virtually instant

58 Three thin filament activation states possessing differential

59 data suggest that the NTE constrains cardiac thin filament activation such that the transition of the

60 We developed a Markov model of cardiac thin filament activation that accounts for interactions

61 XB binding can also amplify thin filament activation through interactions with RUs (

62 XB binding was critical for stabilizing thin filament activation, particularly at submaximal Ca(

63 eedback of force-generating cross-bridges on thin filament activation.

64 dependent change in [Ca(2+) ]-sensitivity of thin filament activation.

65 eletion mutant's ability to modulate cardiac thin-filament activation and Ca(2+) sensitivity.

66 During cardiac thin-filament activation, the N-domain of cardiac tropon

67 pomyosin movement over actin subunits during thin-filament activation, thus reducing both the fractio

68 We focus here on the modulation of thin filament activity by cardiac troponin I phosphoryla

69 This suggests that cMyBP-C might modulate thin filament activity by interfering with tropomyosin r

70 sults suggest that cMyBP-C may both modulate thin filament activity, by physically displacing tropomy

71 erstood, but might involve the length of the thin filament, an important determinant of force generat

72 increases the Ca(2+)-binding affinity of the thin filament and elicits changes in Ca(2+) homeostasis

73 n with that of the calcium activation of the thin filament and find that they are identical but oppos

74 he Ca(2+)-mediated interaction between actin thin filament and myosin thick filament.

75 lymerization, HSPB7 KO mice had longer actin/thin filaments and developed abnormal actin filament bun

76 tein involved in the structural formation of thin filaments and in the regulation of their lengths th

77 inct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the

78 used fluorescent probes on troponin C in the thin filaments and on myosin regulatory light chain in t

79 deno-associated viral transduction elongates thin filaments and rescues structural and functional def

80 region of MyBP-C stabilizes the ON state of thin filaments and the OFF state of thick filaments and

81 Adult HCM patients (age >18 years), 80 with thin-filament and 150 with thick-filament mutations, wer

82 myosin molecule to a single regulated actin thin filament, and separately determined the distance ov

83 there are at least two closed states of the thin filament, and that Tm provides additional points of

84 nity in isolated cTnC, the troponin complex, thin filament, and to a lesser degree, thin filament wit

85 calcium to troponin in the actin-containing thin filaments, and a structural change in the thin fila

86 tin (F-actin) is the major protein of muscle thin filaments, and actin microfilaments are the main co

87 Thus, nebulin regulates thin filament architecture by a mechanism that includes

88 In skeletal muscle, thick and thin filaments are arranged in a myofibrillar lattice.

89 n cytoskeleton and the attached Z-band-bound thin filaments are degraded after ubiquitination by the

90 perative structural changes in the thick and thin filaments are fundamental to the physiological regu

91 the thick filaments that do not overlap with thin filaments are highly disordered during isometric co

92 yosin molecules are required to activate the thin filament arises from an assumption, made during dat

93 Actin-based thin filament arrays constitute a fundamental core compo

94 for studying the assembly and maturation of thin-filament arrays in a skeletal muscle model system.

95 stinct phases in the dynamic construction of thin-filament arrays.

96 NM is thought to be a disease of sarcomeric thin filaments as six of eight known genes whose mutatio

97 The Z-disc is a critical anchoring point for thin filaments as they slide during muscle contraction.

98 licated in the regulation of striated muscle thin filament assembly; its physiological function has y

99 nd tropomyosin-binding protein that controls thin-filament assembly, stability, and lengths.

100 did not displace tropomyosin or activate the thin filament at low Ca(2+) but slowed thin filament sli

101 asure the myosin-based sliding velocities of thin filaments at different pCa, N.k(att), and k(det) va

102 n a slower and less complete deactivation of thin filaments at the end of contractions.

103 on tuning cMyBP-C's calcium-sensitization of thin filaments at the low calcium levels between contrac

104 nin I in a network involving the ends of the thin filaments at the Z-disk and the M-band regions.

105 rdless of Ca(2+), and increases in myosin S1-thin filament ATPase rates in the presence of saturating

106 makes an angle of about 55 degrees with the thin filament axis in relaxed muscle, in contrast with p

107 d azimuthal slew of the lever arm around the thin filament axis, which was not predicted from known c

108 makes an angle of about 45 degrees with the thin filament axis.

109 These data highlight the importance of thin filament-based cooperative mechanisms in cardiac re

110 SL, possibly through reduced availability of thin filament binding sites (cTnI) or altered crossbridg

111 its that Tm exists in three positions on the thin filament: "blocked" in the absence of calcium when

112 ng contraction in a novel way via this thick-thin filament bridge.

113 d by calcium binding to the actin-containing thin filaments but modulated by structural changes in th

114 proaches to track myosin head binding to the thin filament, but is absent in the regulatory head.

115 ction in a unique way--by bridging thick and thin filaments--but there has been no evidence for this

116 rganization on native relaxed cardiac muscle thin filaments by applying single particle reconstructio

117 discovered that Lmod2 functions to elongate thin filaments by promoting actin assembly and dynamics

118 en TNT1 flexibility and the cooperativity of thin filament calcium activation where an increase in fl

119 n linking molecular phenotype to genotype in thin filament cardiomyopathies.

120 in support of a more proximal definition of thin filament cardiomyopathies.

121 s suggested that mutations in the regulatory thin filament caused a complex, heterogeneous pattern of

122 Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congen

123 n filaments in the I-band, where nebulin and thin filaments coalign.

124 myosin fails to localize properly within the thin filament compartment and its expression alters sarc

125 n) is an important regulatory protein in the thin-filament complex of cardiomyocytes.

126 h published intermolecular distances between thin filament components, we derive models of thin filam

127 also resulted in more dynamic populations of thin filament components, whereas expression of mini-neb

128 embly of desmin filaments and destruction of thin filament components.

129 dependent interactions of myosin motors with thin filaments composed of the proteins actin, troponin,

130 The striated muscle thin filament comprises actin, tropomyosin, and troponin

131 e and ATPase activation is possibly due to a thin filament conformation that promotes fewer accessibl

132 Thin filaments containing 50:50 cTnT3-DeltaN100/DeltaE10

133 on from beta-adrenergic signaling as a novel thin filament contractile regulatory signaling mechanism

134 force-generating cross-bridges and shortened thin filaments contribute to the force deficit.

135 elta) + Tm(H276N) fibers, whereas diminished thin-filament cooperativity attenuated tension in McTnT(

136 uated by McTnT45-74, suggesting an effect on thin-filament cooperativity.

137 binding and dissociation within the cardiac thin filament (CTF) is a fundamental regulator of normal

138 relaxation, related to myosin detachment and thin filament deactivation rates, decreased with gestati

139 .68), and was associated with an increase in thin filament density (r = 0.92).

140 est Ca(2)(+) binding to troponin activates a thin filament distance spanning 9 to 11 actins and coupl

141 in-S1 heads that can interact with the actin thin filament during transition from the weakly to the s

142 ld-type or Tmod4(-/-) muscle fibers leads to thin filament elongation by approximately 15%.

143 ativity of calcium response of the regulated thin filaments even in the absence of myosin heads.

144 aced with mini-nebulin in skeletal myocytes, thin filaments extended beyond the end of mini-nebulin,

145 A, D175N, and E180G) were examined using the thin-filament extraction and reconstitution technique.

146 K210, respectively), were examined using the thin-filament extraction/reconstitution technique.

147 anding of the troponin complex on the muscle thin filament, focusing on conformational changes in fle

148 t activation such that the transition of the thin filament from the blocked to the closed state becom

149 us of twitchin also interacts with thick and thin filaments from Mytilus anterior byssus retractor mu

150 in a second to yield a pathogenic change in thin filament function that results in mutation-specific

151 omyosin to F-actin is required for effective thin filament function.

152 ever, recent discoveries of mutations in non-thin filament genes has called this model in question.

153 Studies on muscle from which the thin filaments had been extracted (using the actin sever

154 This suggests that the thin filament has the potential to be turned fully on or

155 ach, the cooperative binding of myosin along thin filaments has been quantified.

156 skeletal muscle in which both the thick and thin filaments have a regulatory function.

157 iphasic LV filling is particularly common in thin-filament HCM, reflecting profound diastolic dysfunc

158 ), and affinity measurements of cTnC for the thin filament in reconstituted papillary muscles to prov

159 ts and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal la

160 We present a model of Ca-regulated thin filaments in cardiac muscle where tropomyosin is tr

161 its localization at the pointed ends of the thin filaments in cardiomyocytes.

162 redundant mechanical link between thick and thin filaments in catch.

163 The longer thin filaments in dogfish account for only part of this

164 the structure and organization of thick and thin filaments in muscle and the interaction of myosin w

165 Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients.

166 nce of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibri

167 essential for the organization of sarcomeric thin filaments in skeletal muscle.

168 (1) used ATPase studies using reconstituted thin filaments in solution to show that these FHC mutant

169 Activation of thin filaments in striated muscle occurs when tropomyosi

170 sarcomeres to control the precise length of thin filaments in the contractile apparatus.

171 pel myosin thick filaments relative to actin thin filaments in the fiber.

172 of Lmod2 in mice results in abnormally short thin filaments in the heart.

173 th in sarcomeres, potentially by stabilizing thin filaments in the I-band, where nebulin and thin fil

174 f muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with t

175 The multiple sites of thin filament interaction in the N terminus of twitchin

176 ges in myofilament spacing (d(1,0)) or thick-thin filament interaction.

177 Calcium binding to thin filaments is a major element controlling active for

178 available to interact with actin-containing thin filaments is controlled by the stress in the myosin

179 We show the strain energy in the thick and thin filaments is less than one third the strain energy

180 ller Z-discs in their core, whilst the thick/thin filament lattice can form peripherally without a Z-

181 emically skinned fibers at various thick and thin filament lattice spacings from four transgenic Dros

182 binding to troponin in the actin-containing thin filaments, leading to an azimuthal movement of trop

183 ever, the precise role of nebulin in setting thin filament length and its other functions in regulati

184 t shock protein in directly modulating actin thin filament length in cardiac muscle by binding monome

185 Nebulin sets actin thin filament length in sarcomeres, potentially by stabi

186 dentify Tmod1 as the key direct regulator of thin filament length in skeletal muscle, in both adult m

187 disappears from soleus muscle, resulting in thin filament length increases of approximately 10 and a

188 lts implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanism

189 whereas Tmod4 appears to be dispensable for thin filament length regulation.

190 uggest that pointed-end assembly and Tmod1's thin filament length regulatory function are regulated b

191 distinct sites in the sarcomere and controls thin filament length with just two nebulin repeats.

192 d that abnormal actin bundles, not elongated thin filament length, were the cause of embryonic lethal

193 ril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1

194 ns (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at p

195 than total sarcomeric Tmod levels, controls thin filament lengths in mouse skeletal muscle, whereas

196 and Lmod3 to control myofibril organization, thin filament lengths, and actomyosin crossbridge format

197 nerate Tmod4(-/-) mice, which exhibit normal thin filament lengths, myofibril organization, and skele

198 , resulting in approximately 11% increase in thin filament lengths.

199 in filament myopathy patients with shortened thin filament lengths.

200 ted to various anisotropy experiments at the thin filament level.

201 ation, coupled to the emerging evidence that thin filament linked cardiomyopathies are progressive, s

202 ted with actin-subunits along the surface of thin filaments, makes electrostatic interactions with cl

203 provides a structural correlate to evaluate thin-filament mechanics, self-assembly mechanisms, and t

204 l muscle cells that, although the well-known thin-filament mechanism is sufficient for regulation of

205 This calcium/thin filament mediated pathway provides the "START" sign

206 es that acts independently of the well-known thin filament-mediated calcium signalling pathway.

207 m levels necessary to maximally activate the thin filament mitigated the structural effects of phosph

208 l, using homogenization theory and atomistic thin filament models from the Protein Data Bank.

209 actin via its N-terminal domains, modulating thin filament motility.

210 anization of troponin and tropomyosin on the thin filament must be determined.

211 In adult HCM patients, thin-filament mutations are associated with increased li

212 cohort of patients with HCM associated with thin-filament mutations compared with thick-filament HCM

213 pared with thick-filament HCM, patients with thin-filament mutations showed: 1) milder and atypically

214 hypertrophic cardiomyopathy (HCM) caused by thin-filament mutations.

215 Thin filament myopathies are among the most common nondy

216 ents, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1

217 he development of therapeutic strategies for thin filament myopathy patients with shortened thin fila

218 eb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanis

219 ensitivity observed in Ca(2+) binding to the thin filament, myosin S1-ADP binding to the thin filamen

220 ecular mechanism of muscle activation in the thin filament-myosin head complex under physiological co

221 ructural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that

222 anges in the conformation of troponin in the thin filaments of skeletal muscle were followed during a

223 ilaments with uniform lengths, including the thin filaments of striated muscles and the spectrin-base

224 , as a primary and versatile mediator of IFM thin-filament organization.

225 discharges since they do not form stratified thin-filament patterns.

226 Lmod2 null background rescued the elongated thin filament phenotype of HSPB7 KOs, but double KO mice

227 perative recruitment of cross bridges to the thin filament: phosphorylation of cardiac myosin binding

228 omodulin (Tmod) isoforms Tmod1 and Tmod4 cap thin filament pointed ends and functionally interact wit

229 vere model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA

230 e are associated with loss of Tmod1 from the thin filament pointed ends, resulting in approximately 1

231 he optimal localization of tropomodulin-1 at thin filament pointed ends, with site 2 acting as the ma

232 by promoting actin assembly and dynamics at thin filament pointed ends.

233 mics in myocytes by acting as a leaky cap at thin filament pointed ends.

234 rationally engineered TnC constructs, three thin filament protein modifications representing differe

235 No changes in thin filament protein phosphorylation were evident.

236 The thin filament protein troponin T (TnT) is a regulator of

237 ntly implicated in NM, as well as a putative thin filament protein, leiomodin 3 (LMOD3).

238 Gelsolin-dependent removal of thin filament proteins also reduced myofilament-bound PK

239 Co-sedimentation of thin filament proteins indicated that no significant cha

240 Loss of sarcomere thin filament proteins is a frequent cause of NM; theref

241 ingly, we find that the rapid destruction of thin filament proteins upon fasting was accompanied by i

242 levels prevented the loss of both desmin and thin filament proteins.

243 Mutations in thin-filament proteins have been linked to hypertrophic

244 Ca(2+) binding to thin filaments reconstituted with either cTnI(wild-type)

245 ility assay to measure Ca(2+) sensitivity of thin filaments reconstituted with recombinant Tpm3.12 De

246 ted the abnormal Ca(2+) sensitivities of the thin filament, reconstituted actomyosin ATPase activity,

247 Our previous understanding of thin filament regulation had been limited to known movem

248 lts provide novel information on how cardiac thin filament regulation is modulated by PAK3 phosphoryl

249 reorganization of the actin cytoskeleton and thin filament regulation to the myogenic response and se

250 uggesting the underlying structural basis of thin filament regulation.

251 herein we propose a novel model of skeletal thin filament regulation.

252 ) domain protein involved in skeletal muscle thin filament regulation.

253 e delicately poised energy balance governing thin filament regulation.

254 Implications for theories of thin-filament regulation in muscle are discussed.

255 ss increases in the apparent affinity of the thin filament regulatory Ca(2+) sites, similar decreases

256 ltaGCIA, the energy barrier for activating a thin filament regulatory unit in the absence of Ca2+.

257 cooperative interactions between neighboring thin filament regulatory units (RU-RU cooperativity; 1 R

258 n by cRLC phosphorylation is mediated by the thin filament, revealing a signaling pathway between thi

259 e the thin filament at low Ca(2+) but slowed thin filament sliding as much as the larger fragments.

260 n tropomyosin position and caused slowing of thin filament sliding.

261 ases in sarcomere length can reduce thick-to-thin filament spacing in skinned muscle fibers, thereby

262 Thick to thin filament spacing was reduced by applying 4% w/v of

263 hin filament components, we derive models of thin filament structure in which the IT arm of troponin

264 t lower calcium levels is due to a change in thin filament structure.

265 ng a significant gap in our understanding of thin-filament structure and regulation.

266 cross-bridge cycling rates slow as thick-to-thin filament surface distance decreases with sarcomere

267 redicts t(on) varies inversely with thick-to-thin filament surface distance, suggesting that cross-br

268 gor myosin is required to fully activate the thin filament (TF).

269 C2) can bind to and activate or inhibit the thin filament (TF).

270 C1mC2 induced larger structural changes in thin filaments than calcium activation, and these were s

271 backbone allowed it to attach more firmly to thin filaments than the wild-type isoform, providing evi

272 in filaments, and a structural change in the thin filaments that allows myosin motors from the thick

273 nge in the structure of the actin-containing thin filaments that allows the head or motor domains of

274 ating the relative sliding between thick and thin filaments that does not involve myosin and which co

275 ealing a signaling pathway between thick and thin filaments that is still present when active force i

276 y stirring nutrient patches into networks of thin filaments that motile bacteria can readily exploit.

277 iding motility suggests that they form long, thin filaments that move rapidly away from a colony, ana

278 gical networks are composed of a meshwork of thin filaments that span large volumes of tissue.

279 ring thick-filament (MYH7mut, MYBPC3mut) and thin-filament (TNNT2mut, TNNI3mut) mutations, and IDCM w

280 of Tm along the actin (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on

281 tin and/or the myosin S2 domain, sensitizing thin filaments to calcium and governing maximal sliding

282 ts in the heart; it is essential for cardiac thin filaments to reach a mature length and is required

283 ults from calcium-activated sliding of actin thin filaments toward the centers of myosin thick filame

284 uctural working stroke in the head pulls the thin filament towards the centre of the sarcomere, produ

285 myosin cross-bridge cycling on actin by the thin filament troponin-tropomyosin complex.

286 ectron microscopy helical reconstructions of thin filaments, troponin density is mostly lost.

287 Tropomyosin (Tm) is an actin-binding, thin filament, two-stranded alpha-helical coiled-coil cr

288 treatment increased crossbridge proximity to thin filaments under all conditions.

289 simulations and experiments, and show that a thinning filament unexpectedly passes through a number o

290 Direct visualization of mutant thin filaments via electron microscopy and 3-dimensional

291 thin filament, myosin S1-ADP binding to the thin filament was significantly affected by the same mut

292 generation that was associated with shorter thin filaments was compensated for by increasing the num

293 creased the Ca(2+) sensitivity of TnC on the thin filament, whereas the dilated cardiomyopathy mutati

294 nt structural change in the actin-containing thin filaments, which permits the binding of myosin moto

295 plex, thin filament, and to a lesser degree, thin filament with myosin subfragment 1.

296 in containing just the linker region bind to thin filaments with about a 1:1 mol ratio to actin and K

297 ificant difference between Ca(2+) binding to thin filaments with cTnI(wild-type) and with cTnI(T144E)

298 f the troponin (Tn) complex or reconstituted thin filaments with or without myosin S1.

299 f muscle differentiation; localized to actin thin filaments, with enrichment near the pointed ends; a

300 proportion to the overlap between thick and thin filaments, with no change in its interference fine