ライフサイエンスコーパス: talin

1 interacts with the major adhesion component, talin.

2 ndependent pathways to undergo activation by talin.

3 r adhesion-related adaptor proteins, such as talin.

4 o bind several ligands, including tensin and talin.

5 activity, and its ability to bind tensin and talin.

6 AP necessary for association with kindlin or talin.

7 the ligand-binding activity of integrins via talin.

8 mine relevant functions of the three ABDs of talin.

9 absent in canonical FERM proteins, including talin.

10 3 in a CHO cell system when coexpressed with talin.

11 pid kinase activity and binding affinity for Talin.

12 F3 region, a critically regulated domain in talin.

13 gulating actin polymerization and binding of talin-1 and kindlin-3 to the beta2 integrin cytoplasmic

14 d stoichiometric quantities of kindlin-3 and talin-1 in platelets and neutrophils, indicating that re

15 hate-interacting adaptor molecule (RIAM) for talin-1 recruitment and thus integrin activation, but di

16 g the existence of alternative mechanisms of talin-1 recruitment.

17 by a mechanism involving the recruitment of talin-1 to the cytoplasmic integrin tail.

18 thermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinit

19 Down-regulated expression of calpain-2 or talin-1, or pharmacological interference with calpain ac

20 s progressively impairs the cooperation with talin-1.

21 signaling, which is induced by kindlin-3 and talin-1.

22 d stoichiometric quantities of kindlin-3 and talin-1.

23 otein ARHGAP10, and the integrin interactors Talin-1/2 or Filamin A.

24 ding and refolding of talin rod domains make talin a very effective force buffer that sets a physiolo

25 Talin, a cytoskeletal protein essential in mediating int

26 its subcellular localization in concert with talin, a cytoskeletal protein targeted to focal adhesion

27 Talin, a force-bearing cytoplasmic adapter essential for

28 Direct methylation of talin, a key regulatory molecule in cell migration, by E

29 The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluores

30 A key modulator of integrin activation is talin, a large cytoskeletal protein that exists in an au

31 Whether talin ABDs regulate actin polymerization in a constituti

32 We found that talin accumulates at the tips of dynamic filopodia, whic

33 ular structure, and implicating the integrin-talin-actin complex as the primary mechanical linkage in

34 ffness stabilizes the assembly of a vinculin-talin-actin scaffolding complex that facilitates PI3K-me

35 function studies in mice have shown that the talin-activating role of RIAM is neither required for de

36 roles in healthy cells, the dysregulation of talin activators can lead to disease states in which abe

37 site and integrins differs, suggesting that talin adopts different orientations relative to integrin

38 Talin also interacts with an additional salt bridge (R73

39 Talin also links integrins to actin and other proteins t

40 ar complex as soon as adhesions are visible; talin, although also present early, associates with the

41 The cytoskeletal protein talin, an actin- and beta-integrin tail-binding protein,

42 ins with cytoplasmic proteins, in particular talin and actin, and cytoskeletal contraction on them ca

43 o the cell membrane and its interaction with talin and actin, which is required for active tension de

44 formation that exposes the binding sites for talin and actin.

45 ng adaptor molecule (RIAM) or lamellipodin), talin and activated integrins in living cells.

46 ur results showed that the interplay between talin and alpha-actinin regulates signal transmission vi

47 Vinculin has binding sites for talin and F-actin, but effective binding requires vincul

48 In addition, blocking calpain cleavage of talin and FAK in vivo promotes Rohon-Beard peripheral ax

49 Blocking calpain cleavage of talin and FAK inhibits repulsive turning from focal unca

50 -based adhesion assembly through cleavage of talin and FAK, and adhesion disassembly through cleavage

51 hesion dynamics through specific cleavage of talin and FAK.SIGNIFICANCE STATEMENT The proper formatio

52 Here, we identify the adhesion proteins talin and focal adhesion kinase (FAK) as proteolytic tar

53 calpain proteolysis of the adhesion proteins talin and focal adhesion kinase.

54 members of the integrin machinery (including talin and integrins) existed before kindlin emergence in

55 scle tissues, where its head domain binds to talin and its tail domain binds to filamentous actin, th

56 sm must be envisioned in which both proteins talin and kindlin are required to produce a productive f

57 How talin and kindlin contribute to these events in non-hema

58 Our findings show that talin and kindlin cooperatively activate integrins leadi

59 mational state and that this requires intact talin and kindlin motifs.

60 ation by presenting the cytoplasmic proteins talin and kindlin to the beta3 cytoplasmic tail.

61 ADAP was physically proximal to talin and kindlin-3 in human platelets, as assessed bioc

62 elet alphaIIbbeta3 through interactions with talin and kindlin-3.

63 oteins involved in alphaIIbbeta3 activation, talin and kindlin-3.

64 rins are two intracellular binding partners, talin and kindlin.

65 M is recruited to immune synapses along with talin and LFA-1, and loss of RIAM profoundly suppresses

66 bi-molecular complex with the head domain of talin and thereby promotes beta3 integrin activation.

67 bound to domains of the cytosolic regulator talin and to extracellular ligands.

68 Furthermore, talin and vinculin association precedes the formation of

69 e demonstrate how the actin-binding proteins talin and vinculin cooperate to provide this link.

70 lar traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and

71 The force-dependent interaction between talin and vinculin plays a crucial role in the initiatio

72 re enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phos

73 egulation of beta1 integrin adhesion through talins and kindlins may differ substantially between sta

74 her and mask the binding sites for actin and talin, and an open activated conformation that exposes t

75 ulin and, to a lesser extent, alpha-actinin, talin, and filamin, to phosphomimetic Cav1Y14D relative

76 Kindlin and talin are both essential for integrin activation based o

77 ation and activation of cytoskeletal protein talin are key steps to initiate the integrin transmembra

78 sition kinetics of the 13 helical bundles of talin are utilized in the diverse talin-dependent mechan

79 Talins are adaptor proteins that regulate focal adhesion

80 Thus, talins are essential for kidney collecting duct developm

81 Our results identify talin as the primary determinant of FA nanoscale organiz

82 ) and together with the cytoskeletal protein talin assemble into a signaling complex upon E-cadherin

83 ermore, we showed that alpha-actinin promote talin association with beta1-integrin by restricting the

84 NAs have formed, myosin II activity promotes talin association with the integrin-kindlin complex in a

85 50I) and VCL(811-1066), both of which arrest talin association.

86 HUTS-21 anti-beta1antibody and by increased talin-beta1 association.

87 l inhibitors, we define here a MAP4K4-moesin-talin-beta1-integrin molecular pathway that promotes eff

88 Together our data indicate that reduction of talin-beta3 integrin binding affinity results in deceler

89 Although talin binding is sufficient for inside-out activation of

90 A final step of integrin activation is talin binding to 2 sites within the integrin beta cytopl

91 We have defined the role of talin binding to the beta1 proximal NPxY motif in the de

92 pairs integrin signaling by both undermining talin binding to the beta3-integrin cytoplasmic tail and

93 How intracellular signals promote talin binding to the integrin tail leading to integrin a

94 c tail and reducing the entropic barrier for talin binding.

95 expressing beta3-GFP-integrins with enhanced talin-binding affinity, we experimentally uncoupled inte

96 ellent fibronectin substrates, high-affinity talin-binding integrins formed adhesions, but normal spr

97 n by itself to localize the membrane and the talin-binding site.

98 due to direct competition with vinculin for talin-binding sites.

99 The second talin-binding wave is associated with clot retraction.

100 xillin adapter recruitment to substrate- and talin-bound integrins.

101 Thus, VCL binding talin, but not Arp2/3, is critical for osteoclast functi

102 grin activation and adhesion, Mn(2+) enabled talin- but not kindlin-deficient cells to initiate sprea

103 ic filopodia, which is lost upon cleavage of talin by active calpain.

104 We show that the talin C terminus binds directly to the moesin band 4.1 E

105 matrix (ECM)-bound integrins cross-linked by talin can be forced apart leading to an elongated orient

106 ns that make up the focal adhesions, such as talin, can exhibit mechanosensing.

107 Membrane binding of talin, captured in unbiased simulations, proceeds throug

108 ndlin-3, it associated with an alphaIIbbeta3/talin complex and enabled kindlin-3 to promote agonist-d

109 ation precedes the formation of the integrin-talin complex.

110 est a model whereby force acting on integrin-talin complexes via ABS3 promotes R3 unfolding and vincu

111 Experiments with truncated forms of talin confirm the mechanosensory role of the talin R3 su

112 Talin contains three actin-binding domains (ABDs).

113 Peripheral talin-deficient Treg cells were unable to maintain high

114 bundles of talin are utilized in the diverse talin-dependent mechanosensing processes remains poorly

115 on of either the talin head or rod domain in talin-depleted cells restores early adhesion formation.

116 e rate of cell migration and also found that talin destabilization affects the usage of different int

117 Talin diagonally spans the FA core, with its N terminus

118 ions reveal two possible orientations of the talin dimer at its C-terminus.

119 emonstrate that the C-terminus region of the talin dimer is flexible mainly at the linker between the

120 nd mode of talin mechanosensing in which the talin dimer itself can adopt different orientations in r

121 Switching between the two talin dimer orientations constitutes a mode of mechanose

122 t leading to an elongated orientation of the talin dimer, and the ECM-bound integrins can be forced t

123 ECM producing a collapsed orientation of the talin dimer.

124 Talins directly bind integrins and are essential for int

125 n independent interaction between pUL135 and talin disrupted cell contacts with the extracellular mat

126 Integrin ligation induces transient talin dissociation and Galpha13 binding to an EXE motif

127 We show that distinct combinations of talin domains are required for each of three different i

128 ole for RIAM in conformational regulation of talin during integrin activation and cell adhesion.

129 tegrin complexes containing kindlin, but not talin, emerge.

130 regulated and a molecular mechanism by which talin enhances tumor cell invasion and metastasis.

131 Here we show structurally that talin-F0 binds to human Rap1b like canonical Rap1 effect

132 mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and

133 Electrostatic analysis shows talin F2F3 to be highly polarized, with a highly positiv

134 f the FA and invadopodia-associated proteins talin, focal adhesion kinase (FAK), and cortactin and re

135 f beta3-integrin, whereas it cooperates with talin for activating integrin alpha5beta1.

136 4K4 to inactivate integrin by competing with talin for binding to beta1-integrin intracellular domain

137 been shown that alpha-actinin competes with talin for binding to the cytoplasmic tail of beta3-integ

138 lin, vinculin, and p130Cas, and they require talin for their formation.

139 A new study reveals that a protein called talin forms a vital link between microtubules and focal

140 Overall, these results shed new light on talin function and constrain models for cellular mechano

141 e findings demonstrate that the mechanism of talin function differs in each developmental context exa

142 in, which disrupts KANK1 binding but not the talin function in adhesion, abrogates the association of

143 best explained by alternative mechanisms of talin function, with talin using one or both of its inte

144 There are two talin genes, Tln1 and Tln2, which encode talin1 and tali

145 Vertebrates contain two talin genes, tln1 and tln2.

146 There are two talin genes, Tln1 and Tln2.

147 We show that the RIAM binding to talin-H sterically occludes the binding of a talin-R dom

148 also binds to the N-terminal head of talin (talin-H), a crucial domain involved in binding and activ

149 otherwise masks the integrin-binding site on talin-H.

150 Talin has attracted great interest in the field of mecha

151 aracterization of the membrane-bound form of talin have prevented us from understanding the molecular

152 The talin head domain consists of four distinct lobes design

153 grin alphaIIbbeta3, co-expression of K2 with talin head domain resulted in robust integrin activation

154 ctivation involves the direct binding of the talin head domain to the switch region 2 sequence of the

155 the binding and interactions of the complete talin head domain with a phospholipid bilayer, using mul

156 coding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH

157 n-related protein) domain, also known as the talin head domain, and a series of helical bundles known

158 adhesions form, but expression of either the talin head or rod domain in talin-depleted cells restore

159 interaction is released, the integrin-bound talin head retains the ability to inhibit actin assembly

160 bserved effects are caused by the release of talin head-rod autoinhibition.

161 New data have implicated a role for talin in diseases that are highly regulated by mechanica

162 We find that talin in focal adhesions is under tension, which is high

163 The requirement for talin in maintaining high IL-2Ralpha expression by Treg

164 In this study, we describe a role for talin in maintaining the homeostasis and survival of the

165 The role of the focal adhesion protein talin in regulating these structures is not known.

166 unactivated platelets, but becomes bound to talin in response to elevated intraplatelet calcium leve

167 ating PC-3 cells, CtsH was co-localized with talin in the focal adhesions.

168 nction of Ena/VASP, alpha5beta1-integrins or talin in the somitic cells abolished the FN pillars, ind

169 T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneou

170 tively, our data suggest a critical role for talin in Treg cell-mediated maintenance of immune homeos

171 a13SR2 is not constitutively associated with talin in unactivated platelets, but becomes bound to tal

172 In contrast, mice lacking talins in the developing ureteric bud developed kidney a

173 ing node at newly formed adhesion sites in a talin-independent manner.

174 Talin induces allosteric rearrangements in integrins tha

175 ew of the integrin adhesome, centered on the talin-integrin interaction, and provide examples of how

176 xamine the roles of two proteins that induce talin-integrin interactions--vinculin and Rap1-GTP-inter

177 ntional binary binding conditions, the Rap1b/talin interaction becomes strong upon attachment of acti

178 pressing a talin1 mutant (W359A) that blocks talin interaction with integrins.

179 rc phosphorylation, facilitated by increased talin interactions with the beta3 cytoplasmic domain, in

180 Talin interacts with beta-integrin tails and actin to co

181 inculin binding, activating ABS2 and locking talin into an actin-binding configuration that stabilize

182 adaptor molecule (RIAM), the recruitment of talin into TCR-induced adhesive junctions, and "inside-o

183 sient by nature, probably due to the lack of talin involvement in FAK activation and the absence of v

184 Talin is a critical adhesion protein and participates in

185 Talin is a large 235-kDa protein composed of an N-termin

186 Talin is a major actin-binding protein that controls bot

187 Here, we show that talin is a substrate for cathepsin H (CtsH), a lysosomal

188 Talin is a ubiquitous, large focal adhesion protein that

189 molecule relative to integrins suggest that talin is able to sense different force vectors, either p

190 Thus, although talin is an essential, shared regulator of all integrin

191 Talin is an integrin adaptor, which controls integrin ac

192 Talin is an intracellular protein that is critical for l

193 vation of transmembrane receptor integrin by talin is essential for inducing cell adhesion.

194 ensing in which the vinculin-binding site of talin is exposed after force-induced stretch of a single

195 Tension on talin is increased by vinculin and depends mainly on act

196 Talin is one well-known intracellular activator, but var

197 the C-terminal actin-binding site (ABS3) in talin is required for adhesion complex assembly, the cen

198 Here, we demonstrate that talin is required for invadopodial matrix degradation an

199 Furthermore, talin is required for mammary tumor cell motility, intra

200 Unlike vinculin, talin is under lower tension on soft substrates.

201 We propose that the talin-KANK1 interaction links the two macromolecular ass

202 specific calpain-resistant point-mutants of talin (L432G) and FAK (V744G), we find that calpain inhi

203 Here, we describe a second mode of talin mechanosensing in which the talin dimer itself can

204 We previously described one mode of talin mechanosensing in which the vinculin-binding site

205 These studies reveal the importance of talin-mediated activation of integrins for renal ischemi

206 logical force range of only a few pNs in the talin-mediated force transmission pathway.

207 ing requires talin recruitment to integrins, talin-mediated integrin activation is dispensable.

208 inin and filamin can directly interfere with talin-mediated integrin activation.

209 ons are mechanosensitive structures in which talin mediates a linkage to actin filaments either direc

210 uctural studies and provide insight into how talin might modulate integrin function.

211 over, disruption of the MRL protein-integrin-talin (MIT) complex markedly impairs cell protrusion.

212 model to investigate vinculin activation by talin modulated by tensile force generated by transient

213 rization model, the rod domain region of one talin molecule binds to the F3 lobe on an adjacent talin

214 plex in a stoichiometry consistent with each talin molecule linking two integrin-kindlin complexes.

215 The different arrangements of the talin molecule relative to integrins suggest that talin

216 molecule binds to the F3 lobe on an adjacent talin molecule, thus achieving the state of autoinhibiti

217 By expressing structure-based talin mutants in talin null cells, we show that while th

218 expressing structure-based talin mutants in talin null cells, we show that while the C-terminal acti

219 esent a reproducible model of membrane-bound talin observed across multiple independent simulations.

220 Our data indicate that docking by talin of the chemokine-activated alpha4beta1 to the acti

221 Without talin or actin polymerization, few early adhesions form,

222 1 Y783A or beta1 Y795A substitutions blocked talin or kindlin binding, respectively, and led to beta1

223 re we report that fibroblasts lacking either talin or kindlin failed to activate beta1 integrins, adh

224 Loss of PIPKIgamma or talin or their interaction impaired EMT and the acquisit

225 ter ovary cells co-expressing alphaIIbbeta3, talin, PAR1, and kindlin-3, it associated with an alphaI

226 We demonstrate that talin plays a key structural role in regulating the nano

227 d thrombus formation, and thus regulation of talin presents a critical node where pharmacological int

228 talin-H sterically occludes the binding of a talin-R domain that otherwise masks the integrin-binding

229 bind to the C-terminal rod domain of talin (talin-R) and promote localizations of talin to the membr

230 Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculi

231 talin confirm the mechanosensory role of the talin R3 subdomain and exclude the possibility that the

232 t its kinase activity and are independent of talin recognition.

233 further show that neutrophil arrest requires talin recruitment to and activation of integrins.

234 r, although neutrophil slow rolling requires talin recruitment to integrins, talin-mediated integrin

235 ng to vinculin and vinculin binding inhibits talin refolding after force is released.

236 PIPKIgamma and talin regulate the stability of E-cadherin transcription

237 G protein (Galpha13) directly interacts with talin, relieves its state of autoinhibition, and trigger

238 However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3.

239 The partial function of some mutant talins requires vinculin, indicating that recruitment of

240 Silencing talin resulted in a decrease in cytosolic pH at invadopo

241 ix adhesions and results in the formation of talin-rich but unstable adhesions.

242 effects of molecular targeting (fibronectin, talin, ROCK), including 'adaptive switching' between Con

243 Mutation of the integrin binding site in the talin rod decreases cluster size.

244 he conserved KN domain in KANK1 binds to the talin rod domain R7.

245 dy provides evidence into how the controlled talin rod domain unfolding acts as a key regulator of ad

246 osed after force-induced stretch of a single talin rod domain.

247 endent stochastic unfolding and refolding of talin rod domains make talin a very effective force buff

248 dent unfolding and refolding kinetics of all talin rod domains.

249 nstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force

250 Force induced unfolding of talin rod subdomains has been proposed to act as a cellu

251 o-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3

252 n to the membrane, which critically controls talin's action, remains elusive.

253 ) that perturbs activation without impairing talin's capacity to link integrins to actin and other pr

254 3 shows SR2 binds directly to the F3 lobe of talin's head domain and competes with the rod domain for

255 vinculin and actomyosin activity help change talin's orientation.

256 munohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in

257 Talins, scaffolding proteins that bind to the membrane p

258 green fluorescent protein-labeled actin and talin shows that P2X7 inhibition alters actin cytoskelet

259 We observed a connection between talin stability and the rate of cell migration and also

260 iew, we present the current understanding of talin structure, its relationship to binding partners, a

261 at RIAM also binds to the N-terminal head of talin (talin-H), a crucial domain involved in binding an

262 nown to bind to the C-terminal rod domain of talin (talin-R) and promote localizations of talin to th

263 e report the development and validation of a talin tension sensor.

264 upstream of components such as integrins and talin that are regulated by both Radil and RIAM.

265 s, we identify the key functional domains of Talin that mediate its response to force.

266 sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertio

267 nt a mechanistic basis for the regulation of talin through Galpha13.

268 Talin (tln) binds and activates integrins to couple extr

269 ubiquitously expressed cytoskeletal protein talin (Tln) is a component of muscle costameres that lin

270 Binding of talin to a membrane-distal NPxY sequence facilitates a s

271 p1-mediated membrane-targeting mechanism for talin to activate integrin.

272 hosphorylation of Akt and the recruitment of talin to beta1 integrins.

273 PKIgamma couples with a cytoskeletal protein talin to control the acquisition of mesenchymal phenotyp

274 dicating that recruitment of vinculin allows talin to duplicate its own activities.

275 migration, by Ezh2 disrupted the binding of talin to F-actin and thereby promoted the turnover of ad

276 fingers.' Formation of the complex requires talin to form a bridge between the MRL protein and the i

277 p1 effector that mediates the recruitment of talin to integrins, thereby supporting their activation.

278 hich RIAM binding to R2R3 initially recruits talin to membranes where it activates integrins.

279 However, the pathway that recruits talin to the membrane, which critically controls talin's

280 talin (talin-R) and promote localizations of talin to the membrane.

281 lecule (RIAM) followed by the recruitment of talin to the plasma membrane.

282 PIPKIgamma and talin together control the adhesion and phosphoinositide

283 that such RIAM-mediated steric unmasking of talin triggers integrin activation.

284 cs of force fluctuation during stretching of talin under physiologically relevant pulling speeds and

285 it as the initial mechano-sensing domain in talin, unfolding at approximately 5 pN, suggesting that

286 ternative mechanisms of talin function, with talin using one or both of its integrin-binding sites.

287 Actin cytoskeleton-linked proteins such as talin, vinculin and filamin function as mechanosensors i

288 ntain the expected molecular markers such as talin, vinculin, and p130Cas, and they require talin for

289 an intermediate state stabilized by partial talin-vinculin association.

290 Talin1(L325R) mice, but not talin(W359A) mice, exhibited a severe bleeding phenotype

291 Talin was found to be approximately 97 nm in length and

292 at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages.

293 other adhesion molecules, alpha-actinin and talin, were also significantly slower in the presence of

294 action, including a single point mutation in talin, which disrupts KANK1 binding but not the talin fu

295 sed by structure-function studies is whether talin, which is critical for all integrin-mediated adhes

296 In accord with this prediction, we find that Talin, which links membrane and cortex, forms such a fro

297 atelets exhibited reduced co-localization of talin with alphaIIbbeta3, and reduced irreversible fibri

298 facilitates a second, weaker interaction of talin with an integrin membrane-proximal region (MPR) th

299 Recombinant analogs of talin with modified lengths recapitulated its polarized

300 Simulations of the complex of talin with the integrin alpha/beta TM helix dimer in a m