ライフサイエンスコーパス: IFT

1 IFT complexes initially accumulate at the base of the ci

2 IFT has been implicated in sensory and motile ciliary fu

3 IFT is regulated primarily by cargo loading onto the IFT

4 IFT relies on molecular motors and IFT complexes that me

5 IFT trains are composed of complexes IFT-A and IFT-B and

6 IFT trains transiently pause through surface adhesion of

7 IFT-B and kinesin are associated to anterograde transpor

8 IFT-based transport of GFP-tubulin is elevated in growin

9 IFT-driven movement of adherent flagella membrane glycop

10 y conserved mechanism involving more than 20 IFT proteins.

11 s in the intraflagellar transport complex A (IFT-A) paradoxically cause increased Shh signaling.

12 tionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and main

13 xes [i.e., intraflagellar transport (IFT)-A, IFT-B, and the BBSome], which together transport protein

14 of COPI, and trace the origins of the IFT-A, IFT-B, and the BBSome subcomplexes.

15 also stabilized IFT-B, but failure in IFT-A/IFT-B interaction within the pool at the base of the fla

16 at IFT-A and the BBSome likely arose from an IFT-B-like complex by intracomplex subunit duplication.

17 al approaches we show that TTC26/DYF13 is an IFT complex B protein in mammalian cells and Chlamydomon

18 In the IFT140(RNAi) mutant, an IFT-A protein essential for retrograde transport, the IF

19 transport routes for cytosolic proteins: an IFT-dependent path along the axoneme, and a passive-diff

20 of Chlamydomonas, we show that cells use an IFT-independent mechanism to breach the diffusion barrie

21 ed link between the cytoplasmic dynein-1 and IFT dynein-2 motors.

22 T trains are composed of complexes IFT-A and IFT-B and cargo adaptors such as the BBSome.

23 It is required for association of IFT-A and IFT-B at the base of the flagellum and flagellar import

24 movement of two protein complexes (IFT-A and IFT-B) driven by specific kinesin and dynein motors.

25 and multisubunit particles, termed IFT-A and IFT-B, that carry cargo into the cilium.

26 Anterograde trains split apart and IFT complexes mix with each other at the tip to assemble

27 ective IFT-A particles enter the axoneme and IFT-B trafficking is severely perturbed.

28 antly, entry of PLD into cilia is BBSome and IFT independent.

29 ew, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, a

30 ght the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases,

31 GFP-tubulin is elevated in growing cilia and IFT trains carry more tubulin.

32 for both ciliary heterotrimeric kinesins and IFT particle genes and clarify the function of kif17, th

33 IFT relies on molecular motors and IFT complexes that mediate the contacts with ciliary car

34 Finally, SSTR3 and IFT movements could be uncoupled by perturbing either me

35 Using a conditional anterograde IFT mutant, we demonstrate that the IFT machinery is not

36 IF3 and IFT88, and KIF3-mediated anterograde IFT is responsible for photoreceptor transition zone and

37 in Chlamydomonas induced rapid, anterograde IFT-independent, cytoplasmic microtubule-dependent redis

38 D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into sma

39 y facilitates the ciliary entry of assembled IFT machinery.

40 required for the ciliary import of assembled IFT particles at the ciliary base.

41 erved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance.

42 ail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17.

43 of alpha-tubulin utilizes diffusion besides IFT.

44 agellar matrix and is actively trafficked by IFT.

45 e in the amount of DRC4 cargo transported by IFT particles, and DRC4 transport is downregulated as ci

46 accumulate locally by diffusion and capture; IFT, in contrast, might be required to transport protein

47 n MDCK cells is dominant-negative and causes IFT protein mislocalization and disrupted ciliogenesis.

48 to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of ci

49 lia, Hedgehog pathway impairment and ciliary IFT accumulations.

50 IFT trains are composed of complexes IFT-A and IFT-B and cargo adaptors such as the BBSome.

51 rectional movement of two protein complexes (IFT-A and IFT-B) driven by specific kinesin and dynein m

52 recognize the length of flagella and control IFT.

53 Decreased IFT-A in these short flagella resulted in aggregates of

54 the flagellum and led to severely decreased IFT injection frequency and flagellar-assembly defects.

55 In the absence of CPLANE, defective IFT-A particles enter the axoneme and IFT-B trafficking

56 In a null mutant, lack of IFT74 destabilized IFT-B, leading to flagella assembly failure.

57 e results support the concept that different IFT proteins are responsible for different cargo subsets

58 locomplex, from the large pool of pre-docked IFT-B complexes, and thus initiates ciliary entry of IFT

59 rs kinesin-2 and cytoplasmic dynein 1b drive IFT particles (protein complexes carrying ciliary compon

60 and further unravel the functional basis for IFT.

61 Mutations in genes coding for IFT components have been associated with a group of dise

62 lution, and we show that it is essential for IFT-B core integrity by mediating interaction between IF

63 us, ODA16, and outer arm dynein interact for IFT of the latter.

64 Our results yield a model for IFT and cargo trafficking in native mammalian cilia and

65 sitive mutation in the anterograde motor for IFT.

66 Unlike dynein-1b, kinesin-II detaches from IFT trains at the tip and diffuses in flagella.

67 DRC4 cargoes dissociate from IFT trains at the tip as well as at various sites along

68 suggest that dissociation of kinesin-II from IFT trains serves as a negative feedback mechanism that

69 Thus, we propose that IFT27 separates from IFT-B inside cilia to promote ARL6 activation, BBSome co

70 During ciliary growth, IFT concentrates soluble tubulin in cilia and thereby pr

71 Yet, some ciliated protists do not have IFT components and, like some metazoan spermatozoa, use

72 Instead, higher IFT velocities arise from an increased likelihood that K

73 How IFT trains attain speeds that exceed the unloaded rate o

74 essential for bone development, however, how IFT proteins regulate Hh signalling in osteoblasts (OBs)

75 IFT protein, IFT27, and offer clues into how IFT cargo is selected and transported.

76 m of multiple trains at the ciliary tip, how IFT trains are remodeled in these turnaround zones canno

77 nsion (IFT) studies have shown a decrease in IFT at the O/W interface from approximately 27mN/m to ap

78 oil 1) also stabilized IFT-B, but failure in IFT-A/IFT-B interaction within the pool at the base of t

79 We demonstrate that actin plays a role in IFT recruitment to basal bodies during flagellar elongat

80 e analysed EVC, EVC2 and Smoothened (SMO) in IFT-A deficient cells.

81 eceptors survive longer compared to those in IFT mutants, which display much weaker basal body mispos

82 However, the functions of individual IFT proteins are mostly unclear.

83 on and function, yet the roles of individual IFT proteins remain unclear.

84 inity comparable with that of the individual IFT subunits.

85 rom disruption of retrograde intraflagellar (IFT) transport of the cilium.

86 This effect is absent in kif3a;IFT double mutants, indicating that IFT proteins have ci

87 dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.

88 fficking, but our understanding of mammalian IFT is insufficient.

89 nt an architectural model for ODA16-mediated IFT of ODAs.

90 Intraflagellar transport (IFT) moves IFT trains carrying cargoes from the cell body into the

91 we reconstituted and purified the nonameric IFT-B core from Chlamydomonas reinhardtii and determined

92 s based on avalanching recapitulate observed IFT dynamics, and we further show that the flagellar Ras

93 ntact promotes the localized accumulation of IFT particles in Chlamydomonas flagella.

94 r to regulate this localized accumulation of IFT.

95 The amount of IFT injection in dynein mutant cells was higher than tha

96 Recent studies reveal that the amount of IFT injection negatively correlates with the length of f

97 phylogenetic evidence for common ancestry of IFT subunits and alpha, beta', and epsilon subunits of C

98 It is required for association of IFT-A and IFT-B at the base of the flagellum and flagell

99 ignalling pathway components, are capable of IFT but with significantly less frequency and/or duratio

100 ike GTPase IFT27/RABL4, a known component of IFT complex B, promotes the exit of BBSome and associate

101 oteins (BBSome) as bona fide constituents of IFT in olfactory sensory neurons, and show that they exi

102 Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of

103 actin is perturbed, the normal dependence of IFT recruitment on flagellar length is lost.

104 The distribution of IFT proteins across eukaryotes identifies the BBSome as

105 n in mammalian cells affects the dynamics of IFT particle movement.

106 ied mechanism that triggers ciliary entry of IFT complexes.

107 t known mechanism directing ciliary entry of IFT complexes.

108 at actin is required for sufficient entry of IFT material into flagella during assembly.

109 the base of the flagellum prevented entry of IFT-A into the flagellum and led to severely decreased I

110 mplexes, and thus initiates ciliary entry of IFT.

111 Expansion of IFT subunits by duplication and their subsequent indepen

112 ase of the flagellum and flagellar import of IFT-A.

113 ely devoid of them, making the importance of IFT to mammalian sperm development unclear.

114 EB1 moved independent of IFT trains, and EB1-FP recovery did not require the IFT

115 riolar functions of Kif3a are independent of IFT.

116 The process controlling injections of IFT proteins into the flagellar compartment is, therefor

117 the IFT complex corroborates involvement of IFT components in vesicle transport.

118 ts tied to the size of the localized load of IFT material awaiting injection at the flagellar base, c

119 gh resorption, we show that an acute loss of IFT-B through cilia decapitation precedes resorption.

120 s have determined the molecular machinery of IFT, but these studies do not explain what regulates IFT

121 ternal reflection fluorescence microscopy of IFT proteins in live cells to quantify the size and freq

122 a(2+) signaling can regulate the movement of IFT particles and is therefore likely to play a central

123 ons act to directly regulate the movement of IFT particles.

124 at cells regulate the extent of occupancy of IFT trains by tubulin cargoes.

125 tionalize several ciliogenesis phenotypes of IFT mutant strains.

126 nslocation within flagella by the process of IFT.

127 ubs that had accumulated large quantities of IFT particle-like material between the doublet microtubu

128 The recruitment of IFT components to basal bodies is a function of flagella

129 e of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components

130 This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt respon

131 ts potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and pr

132 ow that, upon disengagement from the rest of IFT-B, IFT27 directly interacts with the nucleotide-free

133 otors, cannot alone account for the speed of IFT trains in vivo.

134 ere they act to recruit a specific subset of IFT-A proteins.

135 flagella on the basis of the travel time of IFT protein in the flagellar compartment.

136 likely through dominant negative effects on IFT.

137 work identifies the tubulin binding site on IFT trains that is responsible for this cargo transport.

138 pmental Cell illuminate key functions of one IFT protein, IFT27, and offer clues into how IFT cargo i

139 al in dyf13 mutant flagella, unlike in other IFT complex B mutants.

140 ing variants in WDR35, and possibly in other IFT-A components, underlie a number of EvC cases by disr

141 n IFT46, has greatly reduced levels of other IFT-B proteins, and assembles only very short flagella.

142 ter the flagellum and to interact with other IFT-B proteins and its sole expression prevents flagellu

143 ions initiate retrograde transport of paused IFT particles to modulate their accumulation.

144 Intraflagellar transport proteins (IFT) are required for hedgehog (Hh) signalling transduct

145 address this issue, we focused on a putative IFT protein TTC26/DYF13.

146 t that a length-dependent feedback regulates IFT.

147 these studies do not explain what regulates IFT injection rate.

148 The molecular pathways regulating IFT are largely a mystery.

149 in fully formed cilia [19-21] also requires IFT, but direct evidence is lacking.

150 spontaneous suppression of ift46-1 restored IFT-B levels and enabled growth of longer flagella, but

151 sight into the role of D1bLIC and retrograde IFT in other organisms.

152 ghly similar to the characterised retrograde IFT phenotype of Dync2h1.

153 t of the evolutionarily conserved retrograde IFT machinery.

154 (IFT), but it does not eliminate retrograde IFT.

155 C that is absolutely required for retrograde IFT and ciliary assembly.

156 odimer and are both essential for retrograde IFT.

157 addition to its canonical role in retrograde IFT, binds to the tubby-like protein, Tulp3, and recruit

158 rather than the ciliary entry or retrograde IFT transport, of various sensory receptors.

159 particles, and begins processive retrograde IFT in <2 s.

160 This export requires retrograde IFT.

161 mpanied by destabilization of the retrograde IFT dynein motor.

162 t is an integral component of the retrograde IFT dynein.

163 through cytoplasmic action of the retrograde IFT motor and shedding of ciliary ectosomes.

164 Here, we report that the retrograde IFT motor, cytoplasmic dynein 1b, is required in the cyt

165 homodimer is dispensable for distal segment IFT.

166 In complex with several IFT dynein light chains, it is required for correct vert

167 ualized the full range of movement of single IFT trains and motors in Chlamydomonas flagella.

168 All six IFT-A components and their motor protein, DYNC2H1, have

169 6 C-terminus can assemble into and stabilize IFT-B but does not support transport of outer arm dynein

170 conclude that IFT74 is required to stabilize IFT-B; aa 197-641 are sufficient for this function in vi

171 uding part of coiled-coil 1) also stabilized IFT-B, but failure in IFT-A/IFT-B interaction within the

172 ds (aa) of the charged N terminus stabilized IFT-B and promoted slow assembly of nearly full-length f

173 t flagella resulted in aggregates of stalled IFT-B in the flagella.

174 Surprisingly, IFT particle assembly and speed were normal in dyf13 mut

175 preciable change in the interfacial tension (IFT) of SSO, indicating that it was not strongly surface

176 Interfacial tension (IFT) studies have shown a decrease in IFT at the O/W int

177 of motors and multisubunit particles, termed IFT-A and IFT-B, that carry cargo into the cilium.

178 developed indirect immunofluorescence test (IFT).

179 We conclude that IFT velocity is governed by (i) the absolute numbers of

180 We find that IFT-A and the BBSome likely arose from an IFT-B-like com

181 flagellar base, collectively indicating that IFT injection dynamics result from avalanche-like behavi

182 in kif3a;IFT double mutants, indicating that IFT proteins have ciliary transport-independent roles, w

183 mental Cell, Liang et al. (2014) report that IFT is regulated in part by the phosphorylation status o

184 We show that IFT trains are coupled to flagellar membrane glycoprotei

185 amydomonas gliding motility and suggest that IFT plays a major role in adhesion-induced ciliary signa

186 T particles, although evidence suggests that IFT particles also exhibit differential rates of movemen

187 The IFT dynein-2 motor complex that regulates ciliary retrog

188 The IFT machinery is composed of motors and multisubunit par

189 The IFT system consists of three subcomplexes [i.e., intrafl

190 The IFT-B core proteins IFT74 and IFT81 interact directly th

191 Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity.

192 ure to import both the IFT-A complex and the IFT dynein into the flagellar compartment.

193 at this is due to failure to import both the IFT-A complex and the IFT dynein into the flagellar comp

194 s mutant, ift46-1, that fails to express the IFT-B protein IFT46, has greatly reduced levels of other

195 Knowledge of how the IFT subunits interact with their cargo is of critical im

196 Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown

197 thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families.

198 cilium evolution and its frequent loss, the IFT complex behaves as a "last-in, first-out" system.

199 In the mouse, the IFT proteins are very abundant in testis, but we here sh

200 The protocoatomer origin of the IFT complex corroborates involvement of IFT components i

201 ssible explanation for the complexity of the IFT machinery.

202 n the gene encoding the IFT88 subunit of the IFT particle.

203 r35(-/-) cilia, but not to the cilium of the IFT retrograde motor mutant Dync2h1(-/-), indicating tha

204 odularity and structural independence of the IFT subcomplexes.

205 ssed, the higher the overall velocity of the IFT train.

206 bunits of COPI, and trace the origins of the IFT-A, IFT-B, and the BBSome subcomplexes.

207 ns in the gene IFT81, a key component of the IFT-B complex essential for anterograde transport.

208 TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis.

209 gly, the small GTPase IFT27, a member of the IFT-B complex, turns out to be essential for retrograde

210 To elucidate the architecture of the IFT-B complex, we reconstituted and purified the nonamer

211 a frequently lost, modular component of the IFT.

212 order of magnitude greater than that of the IFT.

213 e IFT machinery in a manner dependent on the IFT-A complex.

214 egulated primarily by cargo loading onto the IFT particles, although evidence suggests that IFT parti

215 ins, and EB1-FP recovery did not require the IFT pathway.

216 We conclude that the IFT allows sensitive and specific measurement of circula

217 It has been proposed that the IFT complexes originated from vesicle coats similar to c

218 erograde IFT mutant, we demonstrate that the IFT machinery is not required for regulated SAG1-C65 ent

219 We previously showed that the IFT-A complex, in addition to its canonical role in retr

220 nstream of IFT27 to couple the BBSome to the IFT particle for coordinated removal of patched-1 and Sm

221 tein essential for retrograde transport, the IFT dynein components are found at high concentration at

222 osolic proteins tested primarily utilize the IFT path in the anterograde direction, differences are o

223 We propose a model by which the IFT dynein particle is assembled in the cytoplasm, reach

224 monstrating that CrODA16 associates with the IFT complex with an affinity comparable with that of the

225 se of the flagellum, and associates with the IFT machinery in a manner dependent on the IFT-A complex

226 ition fibres and interacts directly with the IFT-B component DYF-11/IFT54.

227 Thus IFT is essential for the formation but not the maintenan

228 onemes of these neurons show no bias towards IFT kinesin-2 choice, and Kif17 homodimer is dispensable

229 organelle [3-8] by intraflagellar transport (IFT) [9-18].

230 d flagella require intraflagellar transport (IFT) along the axoneme.

231 ought to depend on intraflagellar transport (IFT) and diffusion.

232 that assemble via intraflagellar transport (IFT) and function as signaling hubs on eukaryotic cells.

233 enters cilia as an intraflagellar transport (IFT) cargo and by diffusion.

234 al genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases.

235 codes a subunit of intraflagellar transport (IFT) complex B.

236 The intraflagellar transport (IFT) complex is an integral component of the cilium, a q

237 genes that encode intraflagellar transport (IFT) components and 74 ciliopathy loci to screen 92 unre

238 ntical, to that of intraflagellar transport (IFT) components.

239 Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, su

240 Anterograde intraflagellar transport (IFT) employing kinesin-2 molecular motors has been impli

241 Across eukaryotes, intraflagellar transport (IFT) facilitates cilia biogenesis and cargo trafficking,

242 the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, high

243 grade) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that

244 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanie

245 tor for retrograde intraflagellar transport (IFT) in primary cilia.

246 Intraflagellar transport (IFT) is essential for the elongation and maintenance of

247 Anterograde intraflagellar transport (IFT) is mediated by kinesin motor proteins; however, the

248 Retrograde intraflagellar transport (IFT) is required for assembly of cilia.

249 Intraflagellar transport (IFT) is required for proper function of cilia, although

250 ies and cargoes of intraflagellar transport (IFT) kinesin-2 motors kinesin-II and OSM-3/KIF17 without

251 hout affecting the intraflagellar transport (IFT) kinesin-II.

252 epends on the core intraflagellar transport (IFT) machinery and the associated Bardet-Biedl syndrome

253 Intraflagellar transport (IFT) machinery is required for the assembly and maintena

254 oteins, and on the intraflagellar transport (IFT) machinery.

255 a component of the intraflagellar transport (IFT) machinery.

256 Intraflagellar transport (IFT) moves IFT trains carrying cargoes from the cell bod

257 less pronounced in intraflagellar transport (IFT) mutants and reveals that kif3a has a much broader r

258 a are assembled by intraflagellar transport (IFT) of protein complexes that bring tubulin and other p

259 Moreover, intraflagellar transport (IFT) particle components accumulate in the ciliary shaft

260 cking and entry of intraflagellar transport (IFT) particles, ciliary gating for both membrane and sol

261 two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growt

262 Highly conserved intraflagellar transport (IFT) protein complexes direct both the assembly of prima

263 16, as well as the intraflagellar transport (IFT) protein IFT46, but the molecular mechanism by which

264 xpression of known intraflagellar transport (IFT) protein-encoding loci in Atmin mutant embryos.

265 Intraflagellar transport (IFT) proteins are essential for cilia formation and/or f

266 ment and depend on intraflagellar transport (IFT) proteins for their formation and function, yet the

267 do not require the intraflagellar transport (IFT) system for assembly of their flagella.

268 microtubule-based intraflagellar transport (IFT) to organize intercellular signaling.

269 grade transport of intraflagellar transport (IFT) trains has long been suspected to deliver cargo con

270 Intraflagellar transport (IFT) underpins many of the important cellular roles of c

271 h sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme

272 are facilitated by intraflagellar transport (IFT), a bidirectional protein trafficking along the cili

273 by the process of intraflagellar transport (IFT), a highly conserved mechanism involving more than 2

274 flagella requires intraflagellar transport (IFT), a highly regulated kinesin-based transport system

275 assembly requires intraflagellar transport (IFT), a motile system that delivers cargo from the cell

276 bly is mediated by intraflagellar transport (IFT), and cilia defects disrupt hedgehog signaling, caus

277 city of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT.

278 ry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the

279 lagella depends on intraflagellar transport (IFT), the bidirectional movement of two protein complexe

280 in the absence of intraflagellar transport (IFT), the predominant protein transport system in flagel

281 al for anterograde intraflagellar transport (IFT), was significantly reduced at (tam)Arl13b(-/-) basa

282 and maintained by intraflagellar transport (IFT), whereby the two IFT complexes, IFTA and IFTB, carr

283 ubcomplexes [i.e., intraflagellar transport (IFT)-A, IFT-B, and the BBSome], which together transport

284 n a process termed intraflagellar transport (IFT).

285 t process known as intraflagellar transport (IFT).

286 e for motor-driven Intraflagellar Transport (IFT).

287 d through cilia by intraflagellar transport (IFT).

288 are assembled via intraflagellar transport (IFT).

289 ulations (SLIM) employed an ion funnel trap (IFT) to accumulate ions from a continuous electrospray i

290 which localizes to primary cilia in a Tulp3/IFT-A-dependent manner.

291 raflagellar transport (IFT), whereby the two IFT complexes, IFTA and IFTB, carry cargo via kinesin an

292 , we discuss the various ways eukaryotes use IFT and/or TZ proteins to generate the wide assortment o

293 nts and, like some metazoan spermatozoa, use IFT-independent mechanisms to build axonemes exposed to

294 trograde direction where IFT20 only utilizes IFT, and approximately half of KIF17 and one third of al

295 associated to anterograde transport whereas IFT-A and dynein participate to retrograde transport.

296 ce motility (FSM) as a model to test whether IFT provides force for gliding of cells across solid sur

297 While IFT trains moved processively from one end of the cilium

298 in of the axoneme, moves in association with IFT particles inside Chlamydomonas reinhardtii cilia.

299 ocalised to cilia in puncta, consistent with IFT particles, and physically interacted with WDR34, a m

300 ow that they exist in 1:1 stoichiometry with IFT particles.