ライフサイエンスコーパス: retromer

1 was required for DAT recycling and exit from retromer.

2 nd the cytoplasmic tail of sortilin binds to retromer.

3 that DAT endocytic recycling requires intact retromer.

4 for control of cholesterol distribution via retromer.

5 d at least four have been directly linked to retromer.

6 ded by two cytosolic adaptors termed GGA and retromer.

7 s necessary for the endosomal recruitment of retromer.

8 o the OB membrane requires a functional core retromer.

9 oated with the endosomal retrieval machinery retromer.

10 some biogenesis that also interacts with the retromer.

11 from endosomes to the trans-Golgi network by retromer.

12 Here we demonstrate that the core retromer, a complex involved in protein trafficking, par

13 ivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling.

14 Here, we describe the identification of retromer, a master controller of endosomal recycling [4-

15 Alterations in the function of the retromer, a multisubunit protein complex that plays a sp

16 on these organelles and the function of the retromer, a protein coat responsible for endosome-to-Gol

17 a sorting nexin (SNX) and a component of the retromer, a protein complex mediating retrograde vesicle

18 Without retromer, amino acids no longer stimulate mTORC1 translo

19 tory mechanism that controls the activity of retromer, an evolutionarily conserved sorting device tha

20 olving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide

21 m posit that oligomeric interactions between retromer and associated accessory factors on the endosom

22 of LDs requires lipase associating with core retromer and binding to peroxisomes, which then send the

23 rodomains in vivo and assayed the ability of retromer and ESCRT microdomains to regulate one another.

24 be important regulatory interactions between retromer and ESCRT that balance degradative and recyclin

25 interaction of SORLA with cytosolic adaptors retromer and GGA is required for receptor sorting to and

26 ary, verifying the multifunctional nature of retromer and implying that additional sorting must occur

27 Retromer and its associated sorting nexin, SNX27, phenoc

28 causative genes, with one directly linked to retromer and others causing endolysosomal dysfunction.

29 host scaffold protein VPS29, a component of retromer and retriever complexes critical for endosomal

30 entified novel physical interactions between retromer and the Saccharomyces cerevisiae VPS9-domain Ra

31 lasma membrane of CTLs, as recycling via the retromer and WASH complexes was impaired in the absence

32 , including the vacuolar ATPase proton pump, Retromer, and Commander complexes.

33 mechanism controls cargo selection by yeast retromer, and they establish a functional precedent for

34 Furthermore, we show that retromer- and branched actin-mediated trafficking on ear

35 that Mvp1 promotes Vps1-mediated fission of retromer- and Mvp1-coated tubules that bud from the endo

36 S29s in hetero-hexameric, membrane-attached, retromer arches indicates that VARP will prefer binding

37 We show that the adaptor, GGA1, and retromer are essential to mediate rapid trafficking of p

38 ast, TBC1D5 inhibitory interactions with the retromer are maintained in autophagy-deficient cells, le

39 from endocytosed receptors and identify the retromer as a modulator of beta-arrestin-mediated signal

40 VPS35 and VPS26, two core components of the retromer, as novel regulators of Bcl-xL.

41 unction of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.

42 Our results provide new insights into retromer assembly and underscore the power of using path

43 s to the temporal or spatial coordination of retromer assembly or function.

44 At the same time, retromer associated sorting nexin one (SNX-1) and its bi

45 ficking pathway requires SNX3, but not other retromer-associated cargo binding proteins, such as SNX2

46 Investigating the function of the retromer-associated DNAJ protein Rme-8 in vivo, we demon

47 Retromer-associated endosomes are distributed within den

48 etermined that PC2 binds two isoforms of the retromer-associated protein sorting nexin 3 (SNX3), incl

49 ation of mutants, we verify that loss of the retromer-associated Snx27 cargo adaptor, but notably not

50 Mechanistically, depletion of SNX27 or retromer augments intracellular PTHR signaling in endoso

51 Overall, our data redefine the mechanics of retromer-based sorting and call into question whether re

52 Disruption of retromer binding resulted in a retrograde-sorting defect

53 NX3, and two model cargo proteins, RAB7, and retromer-binding segments of the WASHC2C subunit of the

54 t synthetic peptides containing the HPV16 L2 retromer-binding site and a cell-penetrating sequence en

55 ction, the cellular protein complex known as retromer binds to the L2 capsid protein and sorts incomi

56 n the endosome membrane drives clustering of retromer-bound integral membrane cargo prior to its pack

57 VAP is recruited to retromer budding sites on endosomes via an interaction w

58 cargo-selective complex (CSC) of the fungal retromer by genetic analysis, live cell imaging and immu

59 nsport of IRAP does not require sortilin, as retromer can directly bind to the cytoplasmic tail of IR

60 ation on endosomes, whereas they precede the retromer cargo recognition complex.

61 ) for Rab7, is a high-affinity ligand of the retromer cargo selective complex VPS26/VPS29/VPS35.

62 dulate the binding affinities of Vps26 for a retromer cargo, resulting in corresponding changes in ca

63 al vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent m

64 subdomain as well as for recycling of SNX27-retromer cargoes.

65 s VPS35, a latent cytosolic component of the retromer coat.

66 transport intermediates or whether the same retromer-coated carriers can support both itineraries.

67 ) and activate endogenous Gs-proteins in the retromer-coated compartment that brings them to the TGN.

68 a shared transport vesicles generated from a retromer-coated endosome domain.

69 Wls and beta2AR clearly localize to the same retromer-coated endosome domains, Wls is consistently en

70 t was essential for association of RidL with retromer-coated vacuolar and tubular endosomes.

71 s that VARP will prefer binding to assembled retromer coats through simultaneous binding of two VPS29

72 eted to retromer-positive endosomes, and DAT/retromer colocalization was observed in male mouse dopam

73 The retromer complex acts as a scaffold for endosomal protei

74 ll discuss the structure and function of the retromer complex and its neurobiology, its relevance to

75 een the retrograde transport mediated by the retromer complex and virulence in F. graminearum.

76 For example, mutations in the endosomal retromer complex are implicated in Alzheimer's and Parki

77 Finally, we identify the retromer complex as a gatekeeper, terminating beta-arres

78 WASH functionally interacts with the retromer complex at both early and late phases of macrop

79 and FgVps5 which are analogous to the yeast retromer complex components.

80 PIPKIgammai5 loss disturbs retromer complex connection with Rab7a, which blocks the

81 rafficking secondary to a dysfunction of the retromer complex could be implicated in the pathogenesis

82 The retromer complex facilitates the sorting of integral mem

83 Deficit in retromer complex function secondary to lower levels of o

84 y a process dependent on Arf1-GTP levels and retromer complex function.

85 The highly conserved retromer complex has been linked to cargo retrieval from

86 The SNX27-retromer complex has recently been identified as a major

87 The role of the retromer complex in Fusarium graminearum was investigate

88 ing previously unidentified functions of the retromer complex in plant cells, our work provides unant

89 ng the potential for future targeting of the retromer complex in the treatment of Parkinson disease.

90 The retromer complex is a heterotrimer of VPS29, VPS35, and

91 The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-pla

92 The retromer complex is a multimeric protein complex involve

93 Sangare et al. show that the Toxoplasma retromer complex is essential for parasite viability thr

94 Studies using model organisms show that the retromer complex is involved in specific developmental p

95 The retromer complex is well-known for its role in cargo sor

96 DAT colocalized with VPS35, a subunit of the retromer complex mediating recycling from endosomes, in

97 and trafficking secondary to deficiencies in retromer complex proteins in AD pathogenesis.

98 These findings indicate that an SNX3-retromer complex regulates the surface expression and fu

99 rting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to th

100 ective of the present study is to assess the retromer complex system in DS.

101 We conclude that dysregulation of the retromer complex system is an early event in the develop

102 VPS35 forms a core component of the retromer complex that mediates the retrieval of membrane

103 e with VPS35-RABG3f interaction prevents the retromer complex to endosome anchoring, resulting in ret

104 y endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes

105 Here, we investigated the involvement of the retromer complex, an ancient protein module initially di

106 type I receptor SMA-6 (small-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degr

107 rmation depends on the Rab7/Ypt7-interacting retromer complex, consisting of the sorting nexin dimer

108 Furthermore, disruption of the retromer complex, implicated in recycling from the lysos

109 component of the membrane protein-recycling retromer complex, is the third autosomal-dominant gene a

110 transport pathway that is independent of the retromer complex, late endosomes, and recycling endosome

111 he type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement

112 nclude postsynaptic density proteins and the retromer complex, revealing a link to critical regulator

113 l molecule previously shown to stabilize the retromer complex, supporting the potential for future ta

114 ay from its inhibitory interactions with the retromer complex, thereby enabling retromer recruitment

115 recycling, but also by recycling through the retromer complex, which interacts with Chs3 at a defined

116 in vivo by mutation of key components of the retromer complex, which mediates recycling of cargo from

117 The retromer complex, which recycles the cation-independent

118 nctionally related to the well-characterised retromer complex.

119 omain and serves as a cargo selector for the retromer complex.

120 suggesting that PTHR may directly engage the retromer complex.

121 PI(3)P-binding protein SNX1, a member of the retromer complex.

122 ting nexin, SNX27, which is also part of the retromer complex.

123 Strikingly, when the retromer component Vps26 was depleted at the same time,

124 Using in vivo knockdown of the critical retromer component VPS35, we demonstrate a specific role

125 est that MoVps17 specifically functions as a retromer component with CSC and also plays a distinct ro

126 early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling e

127 Depletion of retromer components enhances progeny production, reveali

128 pecific to SNX-1 and RME-8, as loss of other retromer components SNX-3 and vacuolar protein sorting-a

129 recycling endosomes in the intestine, unlike retromer components that act on early endosomes.

130 Instead, retromer cooperates with the RAB7-GAP TBC1D5 to restrict

131 We observed the retromer core component FgVps35 (Vacuolar Protein Sortin

132 C-based studies revealed that both SNX27 and retromer could directly interact with MT1-MMP.

133 osome maturation, but mediates recycling via retromer-dependent and -independent pathways.

134 uggest that they share a biological pathway, retromer-dependent endosomal trafficking.

135 agosomes during metabolic stress facilitates retromer-dependent GLUT1 trafficking.

136 es and transcytotic vesicles, FGD6 regulates retromer-dependent membrane recycling through its intera

137 -M6PR into endosome transport carriers via a retromer-dependent process is restricted to those tether

138 on that VPS35-DLP1 interaction is key to the retromer-dependent recycling of mitochondrial DLP1 compl

139 Finally, we show that this retromer-dependent retrograde cargo trafficking pathway

140 Loss of TBC1d5 causes defective retromer-dependent trafficking of receptors.

141 In addition, retromer-depleted cells displayed more rapid Bax activat

142 Furthermore, the interaction of RidL with retromer did not interfere with retromer dimerization bu

143 of RidL with retromer did not interfere with retromer dimerization but was essential for association

144 Therefore, retromer does contribute to the retrograde trafficking o

145 Ablation of the retromer does not affect insulin signaling but decreases

146 Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targetin

147 al that lysosomal deficits are attributed to retromer dysfunction induced by altered retromer traffic

148 Retromer dysfunction is associated with neurodegenerativ

149 ctive glutamine depletion, we establish that retromer expression is upregulated by transcription fact

150 er genes VPS35 and VPS26A TFEB regulation of retromer expression therefore supports adaptive nutrient

151 inal PDZ-binding motif of PTHR, wiring it to retromer for endosomal sorting.

152 We propose that mammalian retromer forms a multifunctional membrane coat that supp

153 -penetrating sequence enter cells, sequester retromer from the incoming HPV pseudovirus, and inhibit

154 Retromer function and an interaction with Tom1 allow Tol

155 on the association of genes causing NCL with retromer function and endosomal trafficking, review the

156 in regulating the endo-lysosomal pathway and retromer function and raise the possibility that alterat

157 We conclude that Wash-independent retromer function and the Snx27 cargo adaptor are import

158 the mechanisms by which VPS35 mutations and retromer function contribute to PD pathogenesis are not

159 Accordingly, loss of retromer function impairs the anterograde transport of s

160 spensable for embryogenesis but required for retromer function in aging adults, including for synapti

161 number of recent studies implicate aberrant retromer function in photoreceptor degeneration, Alzheim

162 nd Alzheimer's disease, our understanding of retromer function in the adult brain remains limited, in

163 in trafficking, highlighting key examples of retromer function in vivo.

164 However, the effect of this mutation on retromer function remains poorly characterized.

165 PS35 missense variant led to partial loss of retromer function, which may impact neuronal APP traffic

166 ction, stress responses, O-mannosylation, or retromer function.

167 with CLEAR elements in the promoters of the retromer genes VPS35 and VPS26A TFEB regulation of retro

168 Overall, the Vps35 R524W-containing retromer has a decreased endosomal association, which ca

169 The results indicate that retromer has an intrinsic propensity to form low order o

170 Defects in retromer impair various cellular processes and underlie

171 he CDC-42-associated complex functions after retromer in a distinct organelle.

172 Depletion of retromer in Caenorhabditis elegans reduces mTORC1 signal

173 hese findings demonstrate a key role for the retromer in LTP and provide insights into how retromer m

174 A minor role for retromer in Snc1 recycling can also be observed in singl

175 chanistically independent of any role of the retromer in the production of Abeta from APP.

176 SNX-BARs could cooperate with both SNX27 and retromer in the recycling of ligands encompassing the SB

177 utionarily conserved and unexpected role for retromer in the regulation of mTORC1 activity and longev

178 n this study, we have reexamined the role of retromer in the sequence-dependent endosome-to-trans-Gol

179 Retromer, including Vps35, Vps26, and Vps29, is a protei

180 based sorting and call into question whether retromer indeed functions as a complex of SNX-BAR protei

181 With aging, retromer insufficiency triggers progressive endolysosoma

182 osomal membrane is regulated by a network of retromer-interacting proteins.

183 ics to provide a detailed description of the retromer interactome.

184 Thus, retromer interacts with cargos in a more complex manner

185 The retromer is a conserved endosomal scaffold complex invol

186 Retromer is a heterotrimeric complex that associates wit

187 The retromer is a highly conserved multimeric protein comple

188 Retromer is a membrane coat complex that is recruited to

189 The results support a model whereby SNX3-retromer is a minimally concentrative coat protein compl

190 Retromer is a multi-protein complex that recycles transm

191 A retromer is a multimodular protein assembly critical for

192 Retromer is a peripheral membrane protein complex that c

193 Retromer is a protein assembly that plays a central role

194 Here, we demonstrate that retromer is also required to maintain lysosomal amino ac

195 Retromer is an endosomal sorting device that orchestrate

196 In eukaryotes, the retromer is an endosome-localized complex involved in pr

197 Retromer is an evolutionarily conserved multiprotein com

198 Retromer is an evolutionarily conserved protein complex,

199 We demonstrate that retrograde transport of retromer is impaired, leading to its significant reducti

200 s are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the

201 that the distribution of membrane-associated retromer is predominantly comprised of monomer (~18%), d

202 Here, we demonstrate that retromer is required for the maintenance of normal lysos

203 ons in one or more protein components of the retromer leads to increased accumulation of protein aggr

204 The retromer-linked SNX-BAR proteins comprise heterodimeric

205 rturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)-Bin, Amphiphysin, an

206 Our results reveal the role of Vps29 in retromer localization and function, highlighting require

207 etromer in LTP and provide insights into how retromer malfunction in the mature brain may contribute

208 , our data support a critical role for SNX27-retromer mediated transport of PTHR in normal bone devel

209 CLIC4 selectively modulates retromer-mediated apical transport by negatively regulat

210 membrane (PM) and then back to the Golgi via retromer-mediated endocytic recycling.

211 Therefore, retromer-mediated endosome-to-Golgi retrieval of cation-

212 We suggest that sortilin- and retromer-mediated Glut4 retrieval from endosomes may rep

213 prefers ubiquitylation-deficient Rab7, while retromer-mediated LE recycling benefits from an intact c

214 These results confirm the retromer-mediated model of retrograde HPV entry and vali

215 of the molecular and cellular mechanisms of retromer-mediated protein trafficking, highlighting key

216 tinctly labels the protein and regulates its retromer-mediated recycling by enabling Chs3 to be recog

217 lysosomal defects are not due to compromised retromer-mediated recycling of endolysosomal membranes.

218 ane proteins due to deficient sorting into a retromer-mediated recycling pathway.

219 TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes.

220 Retromer mediates sequence-directed cargo exit from endo

221 as et al. fundamentally question the current retromer model and demonstrate that in mammalian cells,

222 By showing how a retromer mutant leads to altered endosomal sorting of sp

223 Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration.

224 all-6) binds to the retromer complex, and in retromer mutants, SMA-6 is degraded because of its misso

225 Neither deletion of retromer nor the fusion machinery with the vacuole affec

226 The cycling of retromer on and off the endosomal membrane is regulated

227 g with its Golgi/TGN localization, silencing retromer or disrupting Golgi/TGN organization all impair

228 risk factors, with several of them linked to retromer or endosomal trafficking dysfunction.

229 Retromer orchestrates the selection and export of integr

230 Retromer organizes the endosomal sorting pathway in conj

231 eceptor (M6PR), suggesting the impairment of retromer pathway in Parkin-deficient cells.

232 adrenergic receptor (beta2AR), which require retromer physiologically for retrograde transport and re

233 ired for apical localization and mobility of retromer positive carrier vesicles, which mediate the bi

234 However, cocaine increased DAT exit from retromer-positive endosomes significantly.

235 ng internalization, DAT robustly targeted to retromer-positive endosomes, and DAT/retromer colocaliza

236 How then does retromer precisely select its cargos?

237 althy controls were examined for the various retromer protein components using Western blot analysis

238 Knockdown of SNX3 or the core retromer protein VPS35 increased the surface expression

239 Upon loss of retromer, RAB7 expands into the ragulator-decorated amin

240 By modulating the retromer-Rab7a connection, PIPKIgammai5 is also required

241 rting 35 (VPS35) is a major component of the retromer recognition core complex which regulates intrac

242 Retromer recognition core proteins were significantly de

243 These results suggest that VPS9 GEFs promote retromer recruitment by establishing PI3P-enriched domai

244 pletion in autophagy-deficient cells rescues retromer recruitment to endosomal membranes and GLUT1 su

245 with the retromer complex, thereby enabling retromer recruitment to endosome membranes and GLUT1 pla

246 Our findings illustrate how retromer recruits a GAP, which is likely to be involved

247 By targeting endocytic trafficking and retromer recycling to the plasma membrane, we were able

248 y failing to direct full-length APP into the retromer-recycling endosome pathway.

249 These results suggest that the retromer regulates apoptosis by facilitating Bcl-xL's tr

250 tastatic breast cancer cell line MDA-MB-231, retromer regulates the matrix invasion activity by recyc

251 Recent studies have revealed that retromer-related Sorting Nexin family (SNX)-Bin/Amphiphy

252 ed 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and

253 enhances progeny production, revealing that retromer restricts Chlamydia infection.

254 Expression of Vps35 R524W-containing retromer results in the accumulation of intracellular al

255 the data presented in this study reappraise retromer's role in CI-MPR transport.

256 on's diseases, yet little is known about the retromer's role in the mature brain.

257 s effect on mTORC1 activity is not linked to retromer's role in the recycling of transmembrane protei

258 tes on endosomes via an interaction with the retromer SNX2 subunit.

259 pported lipid bilayer, fluorescently labeled retromer, SNX3, and two model cargo proteins, RAB7, and

260 Long-standing hypotheses regarding the retromer sorting mechanism posit that oligomeric interac

261 een components of the sorting nexin 3 (SNX3)-retromer sorting pathway using quantitative single parti

262 a RidL in complex with the human VPS29-VPS35 retromer subcomplex.

263 rate that in mammalian cells, the individual retromer subcomplexes have functionally diverged to orga

264 argo loading, binding of SNX27 to the VPS26A-retromer subunit and endosome-to-plasma membrane traffic

265 Additional deletion of a retromer subunit completely eliminates recycling of Snc1

266 in membrane flux, mediated by silencing the retromer subunit Vps26, or in a model of neurodegenerati

267 ermined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Z

268 The knockout of retromer subunit Vps35 causes an ultrastructural alterat

269 of the vacuolar protein sorting 26A (VPS26A) retromer subunit.

270 lates the phosphorylation state of the Vps26 retromer subunit; mutations engineered to mimic these st

271 VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes f

272 bipartite recycling signal recognized by the retromer subunits, Vps26 and Vps35.

273 d that ES17 targets the VPS35 subunit of the retromer tethering complex, preventing its normal intera

274 mediated by Drs2/Rcy1/COPI, Snx4-Atg20, and retromer that retrieve an exocytic v-SNARE from the endo

275 x comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal

276 show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially ass

277 er, in yeast, the role of Rabs in recruiting retromer to endosomes is less clear.

278 ammalian cells, the efficient recruitment of retromer to endosomes requires the lipid phosphatidylino

279 LA variants lacking binding sites for GGA or retromer to query this concept in the brain.

280 nding sites depending on the cargo, allowing retromer to recycle different membrane proteins.

281 eurons facilitates the trafficking of axonal retromer toward the soma and thus enhances protease tran

282 tions as an adaptor that couples PTHR to the retromer trafficking complex.

283 d to retromer dysfunction induced by altered retromer trafficking in the axon of AD-related mutant hu

284 provides new insights into the regulation of retromer trafficking through retrograde axonal transport

285 g Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking.

286 hrough SNX-BAR heterodimers, but not via the retromer trimer, in a ligand- and activation-dependent m

287 dosomes to the TGN independently of the core retromer trimer.

288 ycling tubules marked by actin/sorting nexin/retromer tubular (ASRT) microdomains.

289 ough independent mechanisms rescues aberrant retromer tubulation and cholesterol mistrafficking.

290 ly giving rise to animals at which point the retromer/VARP/TBC1D5 regulatory network became fully est

291 will discuss the viability of targeting the retromer via pharmacological chaperones or genetic appro

292 At the whole-cell level, knockout of retromer Vps35 subunit reduces lysosomal proteolytic cap

293 Although retromer was discovered over 15 years ago, the mechanism

294 ther, our results demonstrate that the SNX27-retromer-WASH complex directs cargoes to the plasma memb

295 These results reveal a role of PI4P in retromer-/WASH-dependent budding from endosomes.

296 tol-4-phosphate (PI4P) and a perturbation of retromer, which controls the retrograde transport of CI-

297 ly endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating Abeta product

298 sorting nexins (SNXs) 5/6, components of the retromer, which relocalizes SNX5/6 to the inclusion memb

299 The interaction of retromer with distinct VPS9 GEFs could thus link GEF-dep

300 ectly interacts with FAM21, which also binds retromer, within the Wiskott-Aldrich syndrome protein an