ライフサイエンスコーパス: retromer

1 for control of cholesterol distribution via retromer.

2 ded by two cytosolic adaptors termed GGA and retromer.

3 s necessary for the endosomal recruitment of retromer.

4 o the OB membrane requires a functional core retromer.

5 raction with VARP and, consequently, also on retromer.

6 equires a conserved sorting machinery called retromer.

7 that DAT endocytic recycling requires intact retromer.

8 was required for DAT recycling and exit from retromer.

9 nd the cytoplasmic tail of sortilin binds to retromer.

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

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

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

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

14 In addition, increasing retromer abundance suppresses degenerative phenotypes of

15 Retromer, an adaptor complex in the endosome-to-Golgi re

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

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

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

19 or trafficking to the vacuole, including the retromer and ESCRT complexes, prevented Pma1p internaliz

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

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

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

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

24 argo, which enhances membrane association of retromer and initiates cargo sorting.

25 Taken together, these studies implicate retromer and lysosomal pathway alterations in PD risk.

26 ort carriers bud from the endosome coated by retromer and Mvp1, and cargo export is deficient in mvp1

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

28 fficking processes in collaboration with the retromer and sorting nexins, but its in vivo function ha

29 Retromer and TbetaRII associate in the presence or absen

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

31 nexin 5 (SNX5), a component of the mammalian retromer, and D1R in human renal epithelial cells.

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

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

34 ytotoxicity involves raft reorganization and retromer- and ESCRT-mediated vesicular transport and deg

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

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

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

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

39 re we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo

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

41 e results elucidate minimal requirements for retromer assembly on the endosome membrane and reveal ho

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

43 data define the primary molecular defect in retromer assembly that arises from the VPS35(D620N) muta

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

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

46 Retromer-associated endosomes are distributed within den

47 Retromer-associated endosomes contain beta-adrenergic re

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

49 isation of these neurotrophin receptors with retromer-associated sorting nexin 1.

50 simultaneously binds PDZ-binding motifs and retromer-associated VPS26.

51 We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to t

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

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

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

55 Importantly, we find that loss of retromer blocks BMP signaling in multiple tissues.

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

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

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

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

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

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

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

63 umented between Vps10 family members and the retromer coat complex, a key component of the intracellu

64 ly of proteins, as well as components of the retromer coat complex, have been implicated as genetic r

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 tro data mirror the localization of FAM21 to retromer-coated vesicles in cells.

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

73 the trans-Golgi network (TGN) [including the retromer complex (Vps35, Vps26) and its putative recepto

74 The retromer complex acts as a scaffold for endosomal protei

75 we characterized the interaction between the retromer complex and sorLA and determined the role of re

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

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 cles, co-localizes in vesicles with Vps26, a retromer complex component that regulates retrograde tra

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

81 The retromer complex facilitates the sorting of integral mem

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

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

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

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

86 nd, we identify a new role for the mammalian retromer complex in maintaining basolateral plasma membr

87 le for RAB-6.2, its effector LIN-10, and the retromer complex in maintaining synaptic strength by rec

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 Here, we show that the retromer complex is expressed in PRs where it is require

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

96 The retromer complex is well known to mediate retrograde tra

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

98 The retromer complex localizes to endosomal membranes and is

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

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

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

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

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

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

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

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

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

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

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

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

111 ARK17 locus, encoding a key component of the retromer complex, were recently identified as a new caus

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

113 ect interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from

114 VPS35 is a component of the retromer complex, which mediates endosome-to-Golgi retri

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

116 The retromer complex, which recycles the cation-independent

117 suggesting that PTHR may directly engage the retromer complex.

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

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

120 ility via Sorting Nexin1, a component of the retromer complex.

121 s to endosomes through interactions with the retromer complex.

122 and deficiency of the VPS35 component of the retromer complex.

123 aling is instead turned off by the endosomal retromer complex.

124 e sequential action of beta-arrestin and the retromer complex.

125 nctionally related to the well-characterised retromer complex.

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

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

128 Recently, a specific mutation in the retromer component VPS35, VPS35(D620N), has linked retro

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

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

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

132 Depletion of retromer components enhances progeny production, reveali

133 affic of retromer pathway cargo is seen, and retromer components show strong genetic interactions wit

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

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

136 of a dimer of sorting nexins and of the core retromer consisting of vacuolar protein sorting (VPS)26,

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

138 has been implicated in APP transport because retromer deficiency leads to aberrant APP sorting and pr

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

140 ng endocytic itineraries of Crumbs and other retromer-dependent cargo.

141 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HP

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

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

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

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

146 on impaired endosomal F-actin nucleation and retromer-dependent transport.

147 e-to-TGN transport, provide new insight into retromer deregulation in Parkinson disease.

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

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

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

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

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

153 Retromer dysfunction is associated with neurodegenerativ

154 er component VPS35, VPS35(D620N), has linked retromer dysfunction to familial autosomal dominant and

155 regulated by VPS35, a major component of the retromer essential for selective endosome to Golgi retri

156 ata provide a molecular link between reduced retromer expression and increased amyloidogenesis as see

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

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

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

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

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

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

163 With disruption of SNX27 and retromer function linked to synaptic dysfunction and neu

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 recognition at the cargo export stage of the retromer functional cycle.

167 ave been identified in plants, how the plant retromer functions remains elusive.

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

169 Whereas endosome targeting of human retromer has been shown to require Rab7-GTP, targeting o

170 Thus retromer has dual roles in retrograde cargo export and i

171 The retromer has not been previously implicated in virus ent

172 oteins, such as AP-4, ARH, Numb, exomer, and retromer, have also been implicated.

173 Defects in retromer impair various cellular processes and underlie

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

175 to soluble ligand and colocalizes with VPS35 retromer in endosomes.

176 al targets, and suggest that the role of the retromer in infection by other viruses should be assesse

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

178 cating the Vps10 family of receptors and the retromer in physiological intracellular trafficking sign

179 teractions that mediate assembly of the core retromer in plants.

180 , Choy et al. (2014) identify a function for retromer in supporting fast, local delivery of neurotran

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

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

183 tion and, while we implicated a role for the retromer in this regulation, the underlying mechanism re

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

185 tor, DAF-4 (dauer formation-defective-4), is retromer-independent and recycles via a distinct pathway

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

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

188 Retromer is a heterotrimeric complex that associates wit

189 Retromer is a membrane coat complex that is recruited to

190 Retromer is a multi-protein complex that recycles transm

191 Retromer is a protein assembly that plays a central role

192 Furthermore, retromer is also required for the endosomal recruitment

193 Retromer is an endosomal sorting device that orchestrate

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

195 Retromer is an evolutionarily conserved protein complex

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

197 We show that membrane recruitment of retromer is mediated by bivalent recognition of an effec

198 The mechanisms by which retromer is recruited to the endosome and captures cargo

199 Recognition of Ypt7 by retromer is required for its function in retrograde sort

200 well as ionotropic glutamate receptors, and retromer knockdown reduces extrasynaptic insertion of ad

201 After retromer knockdown, although TbetaRII internalization an

202 of retromer to phagosomal membranes, reduced retromer levels, and impaired recycling of phagocytic re

203 The retromer-linked SNX-BAR proteins comprise heterodimeric

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

205 The Scrib module is required for proper retromer localization to endosomes and promotes appropri

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

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

208 We found that VPS35 (retromer)-mediated APP recycling to the TGN was required

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

210 3K and RAB signaling are coupled to initiate retromer-mediated cargo export.

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

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

213 tion and, by revealing functional effects on retromer-mediated endosome-to-TGN transport, provide new

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

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 between the TGN and endosomes, particularly retromer-mediated retrieval of APP from early endosomes

220 in-conjugating enzyme significantly impaired retromer-mediated transport.

221 ASH regulatory complex, a known regulator of retromer-mediated transport.

222 Retromer mediates sequence-directed cargo exit from endo

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

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

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

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

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

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

229 alency enables FAM21 to sense the density of retromer on membranes, allowing coordination of SHRC rec

230 complex and sorLA and determined the role of retromer on sorLA-dependent sorting and processing of AP

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

232 Retromer organizes the endosomal sorting pathway in conj

233 However, defective traffic of retromer pathway cargo is seen, and retromer components

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

235 promotes appropriate cargo sorting into the retromer pathway via both aPKC-dependent and -independen

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

237 We propose that the retromer plays a conserved role in recycling rhodopsins

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

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

240 ains show significantly reduced beclin 1 and retromer protein levels.

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

242 ant APP sorting and processing and levels of retromer proteins are altered in AD.

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

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

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

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

251 mulates in endosomes that are decorated with retromer, revealing an additional role for Rab recogniti

252 In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway,

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

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

255 We report that fission of retromer SNX-BAR-coated tubules from yeast endosomes is

256 ein that localizes to endosomes decorated by retromer SNX-BARs and Mvp1, a SNX-BAR that is homologous

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

258 t, and consequent actin polymerization, with retromer sorting domain organization/maturation.

259 of Ypt7-GTP and requires the Vps5 and Vps17 retromer sorting nexin subunits.

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

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

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

263 3K, SNX3, and the RAB7A GTPase, by the VPS35 retromer subunit.

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

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

266 ming HPV proteins form a stable complex with retromer subunits.

267 We propose that retromer supports a broadly distributed network of plasm

268 larized TbetaRII expression is maintained by retromer/TbetaRII binding and delivery to the common rec

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

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

271 These bivalent interactions prime retromer to capture integral membrane cargo, which enhan

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

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

274 associated with dysfunctional recruitment of retromer to phagosomal membranes, reduced retromer level

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

276 participates in the recruitment of the core retromer to the endosomal membrane by interacting with V

277 hown to require Rab7-GTP, targeting of yeast retromer to the endosome is independent of Ypt7-GTP and

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

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

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

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

282 sition beclin 1 as a link between autophagy, retromer trafficking, and receptor-mediated phagocytosis

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

284 In addition, yeast retromer trimer antagonizes Ypt7-regulated organelle tet

285 The retromer trimer subcomplex is an effector of Rab7 (Ypt7

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 Although retromer was discovered over 15 years ago, the mechanism

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

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

293 nts in the assembly and function of the core retromer, we characterize here Arabidopsis vps26-null mu

294 ith the cargo-selective complex (CSC) of the retromer, where it regulates retrograde sorting from end

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

296 nfection, including multiple subunits of the retromer, which initiates retrograde transport from the

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