Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages

被引：956

作者：

Matsunaga, Kohichi ^{[1
,2
]}

Saitoh, Tatsuya ^{[3
,4
]}

Tabata, Keisuke ^{[1
]}

Omori, Hiroko ^{[1
]}

Satoh, Takashi ^{[3
,4
]}

Kurotori, Naoki ^{[1
]}

Maejima, Ikuko ^{[1
]}

Shirahama-Noda, Kanae ^{[1
]}

Ichimura, Tohru ^{[5
]}

Isobe, Toshiaki ^{[5
]}

Akira, Shizuo ^{[3
,4
]}

Noda, Takeshi ^{[1
]}

Yoshimori, Tamotsu ^{[1
,6
]}

机构：

[1] Osaka Univ, Res Inst Microbial Dis, Dept Cellular Regulat, Suita, Osaka 5650871, Japan

[2] Grad Univ Adv Studies, Dept Genet, Mishima, Shizuoka 4558540, Japan

[3] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan

[4] Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan

[5] Tokyo Metropolitan Univ, Grad Sch Sci, Dept Chem, Tokyo 1920397, Japan

[6] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 04期

关键词：

PHOSPHATIDYLINOSITOL 3-KINASE COMPLEXES; SACCHAROMYCES-CEREVISIAE; TUMOR-SUPPRESSOR; CELL-DEATH; RETROGRADE TRANSPORT; NERVOUS-SYSTEM; MEMBRANE; YEAST; UVRAG; TUMORIGENESIS;

D O I：

10.1038/ncb1846

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Beclin 1, a protein essential for autophagy, binds to hVps34/Class III phosphatidylinositol-3-kinase and UVRAG. Here, we have identified two Beclin 1 associated proteins, Atg14L and Rubicon. Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner, whereas Rubicon binds only to a subpopulation of UVRAG complexes; thus, three different Beclin 1 complexes exist. GFP- Atg14L localized to the isolation membrane and autophagosome, as well as to the ER and unknown puncta. Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation. GFP-Rubicon was localized at the endosome/lysosome. Knockdown of Rubicon caused enhancement of autophagy, especially at the maturation step, as well as enhancement of endocytic trafficking. These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition.

引用

页码：385 / U69

页数：39

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