ライフサイエンスコーパス: ATG8

1 formation through reversible modification of ATG8.

2 ating autophagy through its interaction with Atg8.

3 cluding a five-member gene family expressing ATG8.

4 of each of these functions, ATG1, ATG6, and ATG8.

5 P) cleavage from the autophagic reporter GFP-ATG8.

6 protein Atg11 and the ubiquitin-like protein Atg8.

7 ion, and mRNA levels of the autophagy marker ATG8.

8 each subfamily as well as all six mammalian ATG8s.

9 obilization in cereals, we describe here the ATG8/12 conjugation cascades in maize (Zea mays) and exa

10 TG8 and ATG12, we previously showed that the ATG8/12 conjugation pathways together are important when

11 te either tag, we previously showed that the ATG8/12 conjugation system is important for survival und

12 s loci encoding all components necessary for ATG8/12 conjugation, including a five-member gene family

13 lyzed the conjugation machinery required for ATG8/12 modification in Arabidopsis thaliana with a focu

14 n of autophagy by enhancing the stability of Atg8, a critical autophagy protein.

15 Atg8, a lipid-conjugated ubiquitin-like protein, is requ

16 Atg8, a phosphatidylethanolamine-conjugated protein, was

17 omplex in sec7 cells, are immunolabeled with Atg8, a structural component of autophagosomes.

18 ring stress via the interaction of DSK2 with ATG8, a ubiquitin-like protein directing autophagosome f

19 Moreover, sulfide is able to reverse ATG8 accumulation and lipidation, even in wild-type plan

20 patterns in in vitro extract assays, altered ATG8 accumulation levels, an altered pattern of GFP-ATG8

21 however, although we know that the amount of Atg8 affects the size of autophagosomes, the mechanism f

22 knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation without

23 S, whereas we see an enhanced recruitment of Atg8 and 9 at this site.

24 of these components leads to an increase in Atg8 and a concomitant increase in autophagic activity.

25 ation of the two ubiquitin-fold polypeptides ATG8 and ATG12 to phosphatidylethanolamine and the ATG5

26 jugation of two ubiquitin-like protein tags, ATG8 and ATG12, to phosphatidylethanolamine and the ATG5

27 TG7 E1 required to initiate ligation of both ATG8 and ATG12, we previously showed that the ATG8/12 co

28 ubiquitin-like protein conjugation systems, Atg8 and Atg16, to the phagophore assembly site is affec

29 en required for the efficient recruitment of Atg8 and Atg18 to the site of autophagosome formation an

30 Atg11 at the PAS enhances the recruitment of Atg8 and Atg9 to this site and facilitates the formation

31 COG genes resulted in the mislocalization of Atg8 and Atg9, which are critical components involved in

32 fs1 mutants accumulate the autophagy markers ATG8 and NBR1 independently from EDS1.

33 d upregulation of the phagolysosomal markers Atg8 and p62 was notably reduced in draper mutant flies.

34 Furthermore, Atg36 binds Atg8 and the adaptor Atg11 that links receptors for sele

35 er stress conditions to ensure lipidation of ATG8 and thus autophagy progression in C. reinhardtii.

36 it RPN10, which can simultaneously bind both ATG8 and ubiquitin.

37 cascades that couple the AUTOPHAGY-RELATED8 (ATG8) and ATG12 proteins to their respective targets, ph

38 raction between autophagy-related protein 8 (Atg8) and fatty acid synthase (FAS), a pivotal enzymatic

39 homologue of yeast autophagy-related gene 8 (ATG8), and recruited it to stable microtubules in a MAP1

40 y co-localizes with the autophagosome marker ATG8, and anti-NAP1 identifies autophagosomes in immuno-

41 n of p300 reduces acetylation of Atg5, Atg7, Atg8, and Atg12, although overexpressed p300 increases t

42 sion of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS

43 Mammalian homologs of Atg8 are unmodified in Atg7(-/-) erythroid cells, indica

44 We show that Atg8s are dispensable for autophagosome formation and se

45 fficient to drive accumulation of conjugated Atg8 at the cargo.

46 During autophagy, the amount of Atg8 at the PAS showed a periodic change, indicating the

47 ains two Atg4 (AtAtg4a and AtAtg4b) and nine Atg8 (AtAtg8a-AtAtg8i) genes.

48 Unlike ATG8, ATG12 does not associate with autophagic bodies, i

49 on conjugation machinery in the SUMO, NEDD8, ATG8, ATG12, URM1, UFM1, FAT10, and ISG15 pathways while

50 Mutants of autophagy/mitophagy genes ATG8, ATG18, and ATG32 synthetically interact with CL sy

51 low modeling of a full-length, dimeric (Atg7~Atg8-Atg3)(2) complex.

52 The Atg8 autophagy proteins are essential for autophagosome

53 tion that may confer specific binding to the Atg8-coated autophagosomal membrane on which Atg8 is con

54 s issue of Cell, Nakatogawa et al. show that Atg8 conjugated to PE mediates tethering between adjacen

55 ng a conserved groove in Atg7, important for Atg8 conjugation.

56 ke enzyme Atg12~Atg5-Atg16, which stimulates Atg8 conjugation.

57 Here we show that Atg8 controls the expansion of the autophagosome precurs

58 TG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating th

59 nism, ATG1a is delivered to the vacuole with ATG8-decorated autophagic bodies.

60 cumulation levels, an altered pattern of GFP-ATG8-decorated cellular structures, and altered recovery

61 We demonstrate that the amount of Atg8 determines the size of autophagosomes.

62 concentrations of phosphatidylethanolamine, Atg8 does not act as a fusogen.

63 jugation of the ubiquitin-like protein (UBL) Atg8 during autophagy.

64 ytosis by a murine macrophage cell line, and Atg8 expression was exhibited in WT C. neoformans during

65 ogenesis, a strain of C. neoformans in which Atg8 expression was knocked down by RNA interference was

66 esults clarify the essential function of the Atg8 family and identify GABARAP subfamily members as pr

67 In mammals, the Atg8 family consists of six members divided into the LC3

68 The expansion of the ATG8 family in higher eukaryotes suggests that specific

69 knock-out mice, as did a mutant lacking the Atg8 family interacting motif (AIM) and another mutant t

70 c acid receptor-associated protein (GABARAP) Atg8 family is much less understood than the LC3 Atg8 fa

71 The ATG8 family LC3/GABARAP proteins are attached to the mem

72 Transport of the ATG8 family member GABARAP from the centrosome occurs du

73 GABARAP, but not another ATG8 family member LC3B, binds directly to PCM1 through

74 3 and GABARAP subfamilies as well as all six Atg8 family members in HeLa cells.

75 Members of the Atg8 family of proteins are conjugated to autophagosomal

76 o the autophagosomal membrane decorated with ATG8 family proteins such as LC3B.

77 ns between the ULK complex and six different ATG8 family proteins.

78 family is much less understood than the LC3 Atg8 family, and the relationship between the GABARAPs'

79 e effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and perturbs host-se

80 an IKKgamma does not interact with mammalian Atg8-family proteins.

81 in the N terminus, a domain associated with ATG8-family-specific functions during autophagosome form

82 steine proteases are required for processing Atg8 for the latter to be conjugated to phosphatidyletha

83 During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates

84 ue to ATG4.2 having a key role in removal of ATG8 from mature autophagosomes and thus facilitating de

85 The loss of Atg21 results in the absence of Atg8 from the pre-autophagosomal structure (PAS), which

86 A key component in ATG8 function is ATG12, which promotes lipidation upon i

87 To define Atg8 function, we used genome editing to generate knocko

88 How and when Atg8 functions in this process, however, is not clear.

89 bly, whereas there are only one atg4 and one atg8 gene in the yeast, the mammals have four Atg4 homol

90 Unlike single Atg4 and Atg8 genes in yeast, the Arabidopsis genome contains two

91 Ubiquitin-like ATG8 has been related to both membrane expansion and mem

92 WAC and GM130 interact with the Atg8 homolog GABARAP and regulate its subcellular locali

93 gment reduces coprecipitation with mammalian Atg8 homolog GABARAPL1, suggesting a direct interaction.

94 conjugation) to compare the ability of human ATG8 homologs (LC3, GABARAP, and GATE-16) to mediate mem

95 In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are n

96 autophagic receptor proteins, and mammalian Atg8 homologs.

97 tected for GEC1, but not for other mammalian Atg8 homologs.

98 Mammalian autophagy-related 8 (Atg8) homologs consist of LC3 proteins and GABARAPs, all

99 The Atg8 homologues seem to play different roles in autophag

100 he mammals have four Atg4 homologues and six Atg8 homologues.

101 Atg4 homologues against four representative Atg8 homologues.

102 nts, that two additional sites interact with Atg8 in a LIR-like and thus mutually exclusive manner.

103 We show that Ape1 aggregates bind Atg19 and Atg8 in vitro; this could be used as a scaffold for an i

104 BIN2 phosphorylation of DSK2 flanking its ATG8 interacting motifs (AIMs) promotes DSK2-ATG8 intera

105 in its C terminus in addition to a canonical Atg8-interacting LC3-interacting region (LIR, with LC3 b

106 , with ATG1 tethered to ATG8 via a canonical ATG8-interacting motif.

107 Atg12~Atg5-Atg16 complex is mediated by its Atg8-interacting motifs (AIMs).

108 We have recently discovered ATG8-INTERACTING PROTEIN1 (ATI1) from Arabidopsis thalia

109 two new closely related Arabidopsis thaliana Atg8-interacting proteins (ATI1 and ATI2) that are uniqu

110 The Atg19 receptor contains multiple Atg8 interaction sites in its C terminus in addition to

111 ATG8 interacting motifs (AIMs) promotes DSK2-ATG8 interaction, thereby targeting BES1 for degradation

112 tometry, we demonstrate that enhancing Bnip3-Atg8 interactions via phosphorylation-mimicked LIR mutat

113 Atg8 is a central protein in bulk starvation-induced aut

114 Atg8 is a ubiquitin-like autophagy protein in eukaryotes

115 Atg8 is a ubiquitin-like protein involved in autophagy i

116 Atg8-coated autophagosomal membrane on which Atg8 is concentrated.

117 Similarly, in the sec2 mutant, Atg8 is inefficiently recruited to the phagophore assemb

118 a provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine

119 8) motif, but their mode of interaction with Atg8 is unclear.

120 mutants, development of atg1-1, atg6(-), and atg8(-) is more aberrant in plaques on bacterial lawns t

121 protein fusion of the autophagosome marker, Atg8, is aberrant in both atg1-1 and atg6(-) mutants.

122 core autophagy proteins, including Atg1 and Atg8, is required for LD formation in yeast.

123 Multiple ATG8 isoforms could be detected immunologically in seedl

124 In addition to free ATG8, its membrane-associated, lipidated form was detect

125 he formation of autophagy-related 8-labeled (Atg8-labeled) vesicles and showed a dramatic attenuation

126 nofluorescence for the autophagy protein LC3/Atg8, LC3 electrophoretic mobility shift, mitochondrial

127 We demonstrate here that Atg8/LC3 colocalizes with APP in cultured human muscle c

128 APP/beta-amyloid and Atg8/LC3 double-positive compartments were almost exclus

129 sion to the autophagosome-associated protein Atg8/LC3 led to strongly enhanced MHC class II presentat

130 ATG3 is the E2-like enzyme necessary for ATG8/LC3 lipidation during autophagy.

131 Atg8/LC3 localization was analyzed after GFP-Atg8/LC3 tr

132 RavZ acts by cleaving membrane-conjugated Atg8/LC3 proteins from pre-autophagosomal structures.

133 d after GFP-Atg8/LC3 transfection or with an Atg8/LC3 specific antiserum, respectively.

134 Atg8/LC3 localization was analyzed after GFP-Atg8/LC3 transfection or with an Atg8/LC3 specific antis

135 in expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in toni

136 lls, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macr

137 s autophagosome expansion and recruitment of Atg8/LC3, potentially by decreasing the stability of Atg

138 of APP with the essential autophagy protein Atg8/LC3, which associates with preautophagosomal and au

139 3-phosphate, as well as on the lipidation of Atg8/LC3-like proteins, this area of research has recent

140 These Atg8/LC3-positive phagosomes are formed around the antig

141 In addition, it enhances ATG8/LC3.

142 complex including Sin3 and Rpd3 to regulate Atg8 levels; deletion of any of these components leads t

143 Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles a

144 via interactions with phagophore-associated ATG8-like proteins.

145 ed proteasome subunits/targets and lipidated ATG8 lining the enveloping autophagic membranes.

146 etects the ATG8-PE adduct, we also show that ATG8 lipidation requires the ATG12-ATG5 conjugate.

147 A second conjugation reaction, Aut7/Atg8 lipidation with phosphatidylethanolamine, as well a

148 G8-mediated autophagy in plants by promoting ATG8 lipidation.

149 on of the ATG12-ATG5 adduct is essential for ATG8-mediated autophagy in plants by promoting ATG8 lipi

150 g the Bnip3 LIR promotes binding to specific Atg8 members LC3B and GATE-16.

151 genetically through atg12 mutants that block ATG8 modification.

152 ing region (LIR, with LC3 being a homolog of Atg8) motif, but their mode of interaction with Atg8 is

153 part by an increase in abundance of several ATG8 mRNAs.

154 The atg6(-) and atg8(-) mutants display almost normal development on nit

155 y to interact with both plastid proteins and ATG8 of the core autophagy machinery.

156 ceptors target cargo to autophagy by binding ATG8 on autophagosomal membranes.

157 olar satellites can specifically regulate an ATG8 ortholog, the centrosomal GABARAP reservoir, and ce

158 However, selective interactors of ATG8 orthologs are unknown.

159 tophagy because in its absence the remaining ATG8 orthologs do not support efficient antibacterial au

160 The mammalian ATG8 orthologues (MAP1LC3A/B/C and GABARAP/L1/L2) are ub

161 The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) in

162 the kinetics parameters of the various Atg4-Atg8 pairs provides a base for the understanding of the

163 with a method that unequivocally detects the ATG8-PE adduct, we also show that ATG8 lipidation requir

164 tg18 and Atg21 facilitate the recruitment of Atg8-PE to the site of autophagosome formation and prote

165 Levels of Atg transcripts and/or the ATG8-phosphatidylethanolamine adduct increase during lea

166 ssential for synthesizing the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts that are central t

167 Synthesis of the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts, which are essenti

168 sion of autophagosomes and lysosomes, or the Atg8-processing protein Atg4B.

169 it the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide.

170 led by the amount of Atg8; thus, controlling Atg8 protein levels is one potential mechanism for modul

171 matic residue in Atg8 proteins, producing an Atg8 protein that could not be reconjugated by Atg7 and

172 phagic bodies and immunoblot analysis of the ATG8 protein to show that sulfide (and no other molecule

173 motes the accumulation and lipidation of the ATG8 protein, which is associated with the process of au

174 somal membrane by interacting with lipidated ATG8 proteins (LC3/GABARAP) that are intimately associat

175 n-dependent mitophagy, and cells lacking all ATG8 proteins accumulate cytoplasmic UB aggregates, whic

176 Our data suggest that ATG8 proteins act as scaffolds for assembly of the ULK c

177 phagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete moti

178 Atg8 proteins are localized to the membrane in an ubiqui

179 l effector protein RavZ to directly uncouple Atg8 proteins attached to phosphatidylethanolamine on au

180 hibit autophagy by irreversibly inactivating Atg8 proteins during infection.

181 equent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting reg

182 c activity and is responsible for processing Atg8 proteins near the carboxyl terminus, exposing a con

183 le has the ability to interact with multiple Atg8 proteins simultaneously, resulting in a high-avidit

184 o simultaneously interact with the cargo and Atg8 proteins that coat the membrane.

185 iched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into

186 ULK2, ATG13 and FIP200 interacted with human ATG8 proteins, all with strong preference for the GABARA

187 ophila Atg1 interacted with their respective Atg8 proteins, demonstrating the evolutionary conservati

188 residue and an adjacent aromatic residue in Atg8 proteins, producing an Atg8 protein that could not

189 pecifically acts only on membrane-associated Atg8 proteins, we elucidated its structure.

190 To elucidate the molecular functions of the ATG8 proteins, we engineered cells lacking genes for eac

191 the isolation membrane via interactions with Atg8 proteins.

192 t autophagy proteins engaging only lipidated Atg8 proteins.

193 otease-mediated processing of ubiquitin-like Atg8 proteins.

194 ion of its LC3-interacting region (LIR) with Atg8 proteins.

195 gy, including formation of multiple aberrant Atg8 puncta and drastically impaired autophagosome bioge

196 nown role of S177 phosphorylation in OPTN on ATG8 recruitment, TBK1-dependent phosphorylation on S473

197 sport as determined by localization of a YFP-ATG8 reporter and its vacuolar cleavage during nitrogen

198 response genes (sgkB, csbA, acbA, smlA, and atg8) resulted in altered drug sensitivity, implicating

199 Although Atg8's function in the parasite is not well understood,

200 Following autophagy induction, Atg8 shows the greatest change in expression of any of t

201 which is absolutely conserved in the natural Atg8 substrates.

202 ly induces the autophagy regulators ATG6 and ATG8, sustains ATP levels, and reduces ROS levels to del

203 agy is, in part, controlled by the amount of Atg8; thus, controlling Atg8 protein levels is one poten

204 ed for the conjugation of Atg12 to Atg5, and Atg8 to phosphatidylethanolamine (PE), and is essential

205 ascribed to a reduced rate of conjugation of Atg8 to phosphatidylethanolamine.

206 on pathway that attaches AUTOPHAGY-RELATED8 (ATG8) to phosphatidylethanolamine, which then coats emer

207 We have identified a negative regulator of ATG8 transcription, Ume6, which acts along with a histon

208 by complex molecular systems, including the ATG8 ubiquitin-like conjugation system and the ATG4 cyst

209 h other and with ATG8, with ATG1 tethered to ATG8 via a canonical ATG8-interacting motif.

210 tans RXLR-type effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and per

211 On the basis of the dynamics of Atg8, we present a multistage model of autophagosome for

212 determine the interface between PexRD54 and ATG8, we solved the crystal structure of potato ATG8CL i

213 The autophagy protein LC3/Atg8, which is involved in autophagy membrane traffickin

214 eraction of the Atg12~Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may confer

215 nd ATG13 colocalize with each other and with ATG8, with ATG1 tethered to ATG8 via a canonical ATG8-in

216 ed for autophagosome biogenesis, loss of all Atg8s yields smaller autophagosomes and a slowed initial