ライフサイエンスコーパス: formin

1 st evaluation of diseased-linked variants of formin.

2 tudied the actin assembly properties of this formin.

3 l factors are required to fully activate the formin.

4 o MTs and the induction of Glu MTs by either formin.

5 iants alter actin assembly activities of the formin.

6 hment of profilin to its binding site in the formin.

7 onal drebrin A directly interacts with mDia2 formin.

8 longating barbed ends than most well studied formins.

9 cleation and elongation varies widely across formins.

10 described or systematically studied in other formins.

11 is blocked by inhibitors of both Arp2/3 and formins.

12 n and its interactions with both G-actin and formins.

13 of the mammalian diaphanous (mDia) family of formins.

14 the rate of filament elongation mediated by formins.

15 ed by direct MT binding and interaction with formins.

16 ctin filament growth imposed by profilin and formins.

17 populations of actin filaments to individual formins.

18 encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exo

19 at knockdown of mammalian diaphanous-related formin 1 (mDia1) inhibits chemotactic migration and its

20 1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va

21 We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer'

22 Formin 2 (Fmn2), a member of the FMN family of formins,

23 interacts with the actin-nucleating protein formin 2 (Fmn2).

24 Inverted formin 2 (INF2) is a member of the formin family of acti

25 tin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian

26 Inverted formin 2 (INF2), an actin regulator, mediates a stress r

27 the formin-family actin nucleator, inverted formin 2 (INF2), localizes specifically to FAs and dorsa

28 hored isoform of the formin protein inverted formin 2 (INF2).

29 ng, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS.

30 INF2 (inverted formin 2) is a formin protein with unique biochemical ef

31 study, we investigate the mechanism by which formin-2 (FMN2) orchestrates the initial movement of MI

32 Mutations in the gene encoding inverted formin-2 (INF2), a member of the formin family of actin

33 um- and nuclear membrane-associated inverted formin-2 (INF2), a potent actin polymerization activator

34 Such translocation depends on inverted formin-2 (INF2).

35 Together, our data indicate that Formin-2 is the primary F-actin nucleator during apicomp

36 a comparative approach, we demonstrate that Formin-2, a predicted nucleator of F-actin, is responsib

37 Knockdown of daam1, but not formin-2, resulted in similar disruption of the subapica

38 Profilin release can be directly promoted by formin actin polymerases even at saturating profilin-act

39 As the formin-actin filament has been shown to be part of an as

40 ed on myosin contraction and twisting of the formin-actin filament.

41 Our data highlight a unique mechanism of formin action in which mDia1 and INF2 function in series

42 ilopodia restoration was also induced by the formin-activating molecule IMM-01.

43 Formin activation impairs novel aspects of transformed c

44 with relatively low levels of the canonical formin activator Rho1-GTP.

45 temporal mechanisms used by cells to control formin activities are only beginning to be understood.

46 hasize the importance of tightly controlling formin activities in vivo to generate specialized geomet

47 In summary, our results show that formin activity at epithelial cell-cell junctions is imp

48 Our findings highlight the importance of formin activity in blood vessel morphogenesis.

49 Nuclear formin activity is further required to promote loading o

50 ion of dominant-negative fmnl3 revealed that formin activity maintains a stable F-actin content at EC

51 via modulation of RhoGTPases and downstream formin activity.

52 osition at which profilin is tethered to the formin alters the elongation rate by modulating profilin

53 Formins, an important family of force-bearing actin-poly

54 mutations lead to deregulated activation of formin and a constitutive stress response in cultured ce

55 rolines that are involved in actin assembly (formin and CAP/Srv2p) were significantly reduced by knoc

56 ing components, the Rho effectors diaphanous formin and myosin-II.

57 Consistently, the triple formin and RacE mutants encompassed large peripheral pat

58 Sca2 is structurally unrelated to eukaryotic formins and achieves these functions through an entirely

59 itors, unravel novel functions of Diaphanous formins and add insights into the pathobiology of microc

60 h filaments were simultaneously assembled by formins and disassembled by CCA, these TPM isoform-speci

61 polymerize actin, Smy1 proteins, which bind formins and inhibit actin polymerization, and myosin mot

62 -yet poorly understood, but proteins such as formins and IQGAP1 are known to be involved.

63 contractile ring precursor nodes containing formins and myosin, a new study shows that formin-mediat

64 ted Smy1, which has dual roles in regulating formins and myosin.

65 lly uncoupled Smy1's functions in regulating formins and myosin.

66 re thus tuned to adaptively bridge actin and formins and optimize the rate of actin polymerization.

67 is functionally linked to microtubules with formins and point to formins as major mediators of this

68 trophil extracts and show that activities of formins and the Arp2/3 complex respond to PI(4,5)P(2) la

69 formation revealed that inhibition of Cdc42, formin, and Arp2/3 activities blocked the initiation, bu

70 e into rosettes were also dependent on Rac1, formin, and myosin II activity.

71 tability in cells depleted of the respective formin, and the mDia1-interacting protein IQGAP1 regulat

72 ) is composed of membrane-binding scaffolds, formin, and the tail of the essential myosin-II.

73 mbly pathways, including the Arp2/3 complex, formins, and Ena/VASP, which have largely been analyzed

74 cs within filopodia are under the control of formins, and in particular FMNL2, that binds directly to

75 promoting factors (NEPFs) such as Ena/VASP, formins, and WASP-family proteins recruit profilin:actin

76 the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation.

77 Formins are a conserved group of proteins that nucleate

78 Formins are conserved processive actin-polymerizing mach

79 Formins are conserved regulators of actin cytoskeletal o

80 Thus, while formins are dimeric, Sca2 functions as a monomer.

81 matic cells, we show that actin dynamics and formins are essential for DNA replication.

82 d-end regulators such as capping protein and formins as illustrative examples.

83 ed to microtubules with formins and point to formins as major mediators of this association.

84 Drosophila homolog of the FHOD sub-family of formins, as a primary and versatile mediator of IFM thin

85 raction with the polyproline (Poly-P) of the formin AtFH1.

86 he FH1-FH2 domain of an Arabidopsis thaliana formin, AtFH14, processively attaches to the barbed end

87 a small actin-binding protein that promotes formin-based actin polymerization and regulates numerous

88 These results indicate that formin-based linear actin polymerization is critical for

89 Inhibition of linear, formin-based nucleation with the small-molecule inhibito

90 t it are illustrated with the example of the Formin binding protein 28 (FBP28) WW domain, which folds

91 monomer binds more tightly to profilin, and formin binding suppresses nucleation and slows polymeriz

92 Disrupting either Spire1C actin- or formin-binding activities reduces mitochondrial constric

93 perimentally tuneable parameters such as the formin-binding affinity of Smy1 and the concentration of

94 We show that a novel isoform of the formin-binding, actin-nucleating protein Spire, Spire1C,

95 es not induce the K113:E195 interaction when formin binds to actin K118 and E117 residues located at

96 yosins (Tpm1 and Tpm2), profilin (Pfy1), and formins (Bni1 and Bnr1) are required for the assembly of

97 dependent of its functions in regulating the formin Bnr1, binds to actin filaments and organizes acti

98 inhibitory effects on the FH2 domain of the formin Bnr1.

99 s a mechanosensor, whereby myosin pulling on formin-bound actin filaments inhibits Cdc12-mediated act

100 ology 2 domain-containing protein 1 (FHOD-1) formin bundling.

101 ation was dramatically reduced by inhibiting formins but, surprisingly, accelerated by inhibiting Arp

102 ffold that facilitates the activation of one formin by another.

103 Although the activation of formins by Rho proteins is well characterized, its inact

104 , which is intriguing since variants in both formins cause NS.

105 ll-Release from precursor nodes that include formin Cdc12 and myosin Myo2.

106 ch-Capture-Pull in vitro, we discovered that formin Cdc12 is a mechanosensor, whereby myosin pulling

107 cells established that mechanoregulation of formin Cdc12 is required for efficient contractile ring

108 tributes to CR formation and cytokinesis via formin Cdc12 recruitment, defining a novel cytokinetic f

109 9-Mut) is the ability to enhance cytokinesis formin Cdc12-mediated actin assembly in vitro, which all

110 II myosin Myo2 and the actin assembly factor formin Cdc12.

111 tion of F-actin for the CR requires a single formin, Cdc12, that localizes to the cell middle at mito

112 GTPase-activating protein (IQGAP) Rng2p, and formin Cdc12p form the base of the node that anchors the

113 Formins comprise a large family of proteins with diverse

114 ng TIRF microscopy and constitutively active formin constructs tagged with fluorescent protein.

115 y domain-containing protein (FHOD) family of formins contributes to contractility of striated muscle

116 Therefore, actin dynamics and formins control DNA replication by multiple direct and i

117 ng AFM force-clamp experiments, we show that formin controlled by RhoA switches the actin catch-slip

118 This formin cooperates with profilin and Spire, a WASP homolo

119 ortex is regulated by the single cytokinesis formin CYK-1 and the ARP2/3 complex, which nucleate nonb

120 sprouting in vitro requires profilin and the formin DAAM, but not Ena.

121 e here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-res

122 mutants by aberrant filopods, induced by the formin dDia2.

123 of the actin nucleating factors, Arp2/3 and formin, decreases BCR mobility.

124 The formin Delphilin binds the glutamate receptor, GluRdelta

125 Expansion of the umbrella cell AJR required formin-dependent actin assembly, but was independent of

126 zation was driven by formation of Arp2/3 and formin-dependent actin protrusions that wrapped around t

127 ansmitted to the tip through actin core in a formin-dependent fashion is required for filopodia adhes

128 a 30-kPa Ecad-Fc PA gel required Cdc42- and formin-dependent filopodia formation, whereas adhesion t

129 n vitro, active Pfn1 promoted MT growth in a formin-dependent manner, whereas localization of MTs to

130 m1 works in concert with profilin to promote formin-dependent nucleation of actin cables, thus expand

131 basally constricted neuroepithelia, a novel formin-dependent pushing mechanism is found for which we

132 ediated activation of the Diaphanous-related formin (DIAPH1) and targets DIAPH1 to the plasma membran

133 EEF1A in cadherin contact maintenance is the formin DIAPH2, which interacts with EEF1A.

134 Formins direct the elongation of unbranched actin filame

135 ically, in cells, SPIN90 appears to favour a formin-dominated cortex.

136 Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by con

137 m, we show that the three Diaphanous-related formins (DRFs) ForA, ForE, and ForH are regulated by the

138 Formins drive cable formation by promoting actin nucleat

139 is a switch in a mode of actin assembly from formin-driven to Arp2/3-mediated via an undefined mechan

140 is supported by the observation that an anti-formin drug treatment converts dextral snail embryos to

141 ndritic actin networks, with factors such as formins elongating these filaments into filopodia.

142 Because the formin family is large, with at least 15 members in vert

143 Inverted formin 2 (INF2) is a member of the formin family of actin assembly factors.

144 ng inverted formin-2 (INF2), a member of the formin family of actin regulatory proteins, are among th

145 s a unique microtubule-binding member of the formin family of cytoskeletal-remodeling proteins.

146 FMNL3 is expressed more widely and is a formin family protein that is involved in the regulation

147 zing machines, we locate five members of the formin family to specific regions of the wave landscape

148 The formin-family actin filament nucleator FMN2 associates w

149 Here we show that the formin-family actin nucleator, inverted formin 2 (INF2),

150 localize around the Golgi apparatus with the formin-family protein Diaphanous, and loss of either iso

151 le inhibitor SMIFH2 or overexpression of the formin FH1 domain resulted in formation of predominantly

152 very from the multiple polyproline tracts in formin FH1 domains.

153 Here, we used Small Molecule Inhibitor of Formin FH2 (SMIFH2), after validating its mode of action

154 solution microscopy revealed the presence of formin FHOD1 and INF2-mediated unbranched radial F-actin

155 ependent regulator of actin remodelling, the formin FHOD1, largely rescued morphology in mutant cells

156 n and phenotypic analysis indicated that the formin FHOD3 played a role in this motility but not mDia

157 Spir and formin (FMN)-type actin nucleators initiate actin polyme

158 d three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization,

159 Another actin polymerase, the formin FMNL2, cannot substitute for CP, showing that pol

160 fission yeast Schizosaccharomyces pombe, the formin For3 nucleates actin cables and also co-operates

161 Formin ForB favors the actin wave and ForG the inner ter

162 we analyzed the effects of a set of distinct formin fragments and VASP on site-specific, lamellipodia

163 regulatory proteins and relies on only three formins (FRMs) to nucleate and polymerize actin.

164 is the direct demonstration of a processive formin from plants.

165 mposed of parallel actin cables nucleated by formins from the plasma membrane [4].

166 of fmnl3 expression, chemical inhibition of formin function, and expression of dominant-negative fmn

167 In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is

168 Here, we show that the Diaphanous-related formin G (ForG) from the professional phagocyte Dictyost

169 ults reveal how synergy between profilin and formins generates robust filament growth rates that are

170 domonas expresses a profilin (PRF1) and four formin genes (FOR1-4), one of which (FOR1) we have chara

171 ition or overexpression by microinjection of formin has a chirality-randomizing effect in early (pre-

172 Formins have a conserved formin homology 2 domain, which

173 tory domain (DAD) and the C terminus (CT) of formins have also been shown to regulate actin assembly

174 Additionally, most formins have conserved domains that regulate actin assem

175 nfluencing filament growth together with the formin homology 1 (FH1) domain.

176 ally load actin monomers onto their flexible Formin Homology 1 (FH1) domains.

177 hich then bind polyproline tracts located in formin homology 1 (FH1) domains.

178 The conserved formin homology 1 and 2 (FH1-FH2) domains of DAAM cataly

179 ring, and thereby may stretch the disordered formin homology 1 domain and impede formin-mediated acti

180 We mapped Cdc12 mechanoregulation to its formin homology 1 domain, which facilitates delivery of

181 rcular RNAs derived from Ttn (Titin), Fhod3 (Formin homology 2 domain containing 3), and Strn3 (Stria

182 Formins have a conserved formin homology 2 domain, which nucleates and associates

183 relayed by actin-severing proteins and from formin homology 2 domain-containing protein 1 (FHOD-1) f

184 teracts with the C-terminal extension of the formin homology domain 2 (FH2) domain of Fmn2, called FS

185 ing to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and

186 Among them, the formin homology domain-containing protein (FHOD) family

187 gulation of planar cell polarity through the Formin homology protein Daam.

188 around two actin subunits, analogous to the formin homology-2 domain.

189 ter validating its mode of action on a plant formin in vitro, and observed a reduced nucleation frequ

190 ed disruption of genes encoding mDia1 and -3 formins in B16-F1 mouse melanoma cells revealed enhanced

191 sis of the localization of all 15 vertebrate formins in epithelial cells and suggests that misregulat

192 we characterized the localization of all 15 formins in epithelial cells of Xenopus laevis gastrula-s

193 Delphilin is distinct from other formins in several ways: its expression is limited to Pu

194 Sca2 mimics eukaryotic formins in that it promotes both actin filament nucleati

195 inhibitor SMIFH2 supports the implication of formins in their generation.

196 ation under confinement on laminin relies on formins, including FHOD3, but not Arp2/3 and that the lo

197 c reticulum (ER) targeting the ER-associated formin INF2 at the inner nuclear membrane (INM).

198 and cyclase-associated protein inhibits the formin INF2 by enhancing intramolecular inhibitory inter

199 r results indicate an important role for the formin INF2 in specifying the function of fibrillar FAs

200 Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the en

201 EXC-6, an ortholog of the disease-associated formin INF2, coordinates cell outgrowth and lumen format

202 show that EXC-6 is orthologous to the human formin INF2, which polymerizes filamentous actin (F-acti

203 cytoplasmic actin polymerization through the formin INF2, with downstream effects on ER-to-mitochondr

204 ac1/Cdc42 and their effectors, including the formin INF2.

205 Here we show that another formin, INF2, is necessary for mDia1-mediated induction

206 nctions through CDC-42 to regulate two other formins: INFT-2, another INF2 ortholog, and CYK-1, the s

207 In proliferating cells, formin inhibition abolishes nuclear transport and initia

208 AFs rescued the vimentin collapse, while pan-formin inhibition with SMIFH2 promoted vimentin collapse

209 We used the formin inhibitor SMIFH2 and mDia agonists IMM-01/-02 and

210 Annihilation of the patterns by 1 uM of the formin inhibitor SMIFH2 supports the implication of form

211 rf1-1 mutants, as well as the small molecule formin inhibitor SMIFH2, prevent fertilization tubule fo

212 Formin inhibitor SMIFH2, which causes detachment of acti

213 n arcs, and arc generation was arrested by a formin inhibitor.

214 Anillin, formins, IQGAPs, and many other proteins regulate the as

215 when the filamentous dynamic actin nucleator formin is inhibited.

216 of a tandemly duplicated, diaphanous-related formin is perfectly associated with symmetry breaking in

217 filament nucleators, the Diaphanous-related formins, is activated by the binding of small G-proteins

218 on, and myosin motors, which deliver Smy1 to formins, leading to a length-dependent actin polymerizat

219 We identify formin-like 2 (FMNL2) as being specifically required for

220 , the actin nucleator and elongation factor, formin-like 3 (fmnl3), localizes to EC junctions, where

221 The formin-like protein INF2 is an important player in the p

222 We developed a new Formin-like-1 (FMNL1) knock-out mouse model and determin

223 not been any comprehensive studies examining formin localization and function within a common cell ty

224 thelial cells and suggests that misregulated formin localization results in epithelial cytokinesis fa

225 has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an

226 plex' in which a CP dimer and a dimer of the formin mDia1 simultaneously bind the barbed end.

227 Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects th

228 ) in NIH3T3 fibroblasts through RhoA and the formin mDia1.

229 actin nucleators: the Arp2/3 complex and the formin mDia1.

230 Here, we identify the formin mDia2 as essential for stable replenishment of ne

231 Thus, the formin mDia2 functions downstream of the MgcRacGAP-depen

232 ere, we show that loss of diaphanous-related formin mDia2 leads to impaired engraftment of long-term

233 teins, including tubulin, cortactin, and the formin mDia2, regulates both cytoskeletal assembly and s

234 In diverse biological systems, formins mediate polarized trafficking through the genera

235 posed of actin filament bundles nucleated by formins, mediate intracellular transport for cell polari

236 le of profilin is to specifically facilitate formin-mediated actin assembly for cytokinesis in fissio

237 ggest evolutionarily conserved functions for formin-mediated actin assembly in actin cortex mechanics

238 ing modulate their interactions to fine-tune formin-mediated actin assembly.

239 We previously demonstrated formin-mediated actin dynamics at the rear of the invadi

240 sordered formin homology 1 domain and impede formin-mediated actin filament elongation.

241 properties of actin filaments by modulating formin-mediated actin nucleation and assembly during pla

242 Here we investigated a role for formin-mediated actin polymerization at cell-cell juncti

243 h canonical profilin isoforms in suppressing formin-mediated actin polymerization during plant innate

244 Junction remodeling also requires formin-mediated E-cadherin clustering and dynamin-depend

245 ate profilin's role as an adaptor protein in formin-mediated elongation, we engineered a chimeric for

246 is competition ultimately limits the rate of formin-mediated elongation.

247 of both myosin-II activation and diaphanous formin-mediated filamentous actin (f-actin) assembly, wh

248 Drebrin inhibits formin-mediated nucleation of actin and abolishes mDia2-

249 g formins and myosin, a new study shows that formin-mediated polymerization is strongly inhibited upo

250 Formin-mediated SF elongation negatively feeds back with

251 This formin mediates slow filament elongation owing to a high

252 actin, involving ATP hydrolysis, N-WASP and formin, mediates Omega-profile merging by providing suff

253 ch causes detachment of actin filaments from formin molecules, produces similar effect.

254 ly, live cell imaging of mechano-insensitive formin mutant cells established that mechanoregulation o

255 ence that the delays are due to an excess in formin-nucleated cortical F-actin, suggesting that the A

256 Single or double formin-null mutants displayed only moderate defects in c

257 ulations within the network by, for example, formins or Ena/VASP family members and its influence on

258 reas the concurrent elimination of all three formins or of RacE caused massive defects in cortical ri

259 In this paper, we show that this formin organizes a specific actin structure-the actin fu

260 n vitro motility assays of beads coated with formins, our model allowed us to characterize conditions

261 activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways.

262 bility altered in response to actin, myosin, formin perturbations, or a transcriptional down-regulati

263 rmin 2 (Fmn2), a member of the FMN family of formins, plays an important role in early development.

264 Formins polymerize actin filaments for the cytokinetic c

265 In Saccharomyces cerevisiae, formin-polymerized actin cables are spatially organized

266 Formins processively elongate filaments, whereas capping

267 ily conserved S. cerevisiae proteins (actin, formin, profilin, tropomyosin, capping protein, cofilin,

268 morphogenesis (DAAM) is a diaphanous-related formin protein essential for the regulation of actin cyt

269 merization by the ER-anchored isoform of the formin protein inverted formin 2 (INF2).

270 INF2 is a formin protein that accelerates actin polymerization.

271 INF2 (inverted formin 2) is a formin protein with unique biochemical effects on actin.

272 test whether profilin cooperates with plant formin proteins to execute actin nucleation and rapid fi

273 inding to both monomeric actin (G-actin) and formin proteins.

274 The mechanism by which diverse formins regulate actin dynamics in plants is still not w

275 Multiple formins regulate microtubule (MT) arrays, but whether th

276 cular to the stretch vector are dependent on formin-regulated actin polymerization.

277 A common mechanism for formin regulation is autoinhibition, through interaction

278 ipated mechanistic ties between two distinct formin regulators.

279 results provide important insights into how formin senses these mechanical constraints and regulates

280 Finally, Delphilin is the first formin studied that is not regulated by intramolecular i

281 INF2 also modulates activity of other formins, such as the mDIA subfamily, and promotes stable

282 However, RhoA only partially activates formins, suggesting that additional factors are required

283 roborate reported observations that RhoA and formin switch force-induced actin cytoskeleton alignment

284 ediated elongation, we engineered a chimeric formin that binds actin monomers directly via covalent a

285 Mutants of either formin that disrupt their interaction failed to rescue M

286 gation factors Ena and profilin, but not the formins that are expressed in gamma-neurons.

287 diated in part through its interactions with formins that in turn bind microtubules [3, 4].

288 fission yeast ring revealed that myosins and formins that nucleate actin filaments colocalize in plas

289 Fission yeast cells use Arp2/3 complex and formin to assemble diverse filamentous actin (F-actin) n

290 associated protein CLIP-170 binds tightly to formins to accelerate actin filament elongation.

291 ishes that Fhod shares the capacity of other formins to nucleate and bundle actin filaments but is no

292 he ability of major actin assembly proteins, formins, to sustain actin polymerization.

293 ial for the spatial patterning of cyclin and formin transcripts in cytosol.

294 Because INF2 is a formin-type actin nucleator, research has focused on its

295 these proteins bind actin monomers directly, formins use the actin-binding protein profilin to dynami

296 Surprisingly, expression of formin variants but not VASP reduced lamellipodial protr

297 n regulatory proteins cofilin, profilin, and formin, which sever, recycle, and assemble filaments, re

298 enna mechanism" involves three key proteins: formins, which polymerize actin, Smy1 proteins, which bi

299 gen extraction also requires the activity of formins, which reside near the foci and produce the inte

300 erol promotes the cooperative interaction of formins with multiple PI(4,5)P(2) headgroups in the memb