Article abstract
Nature Cell Biology 11, 385 - 396 (2009)
Published online: 8 March 2009 | doi:10.1038/ncb1846
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages
Kohichi Matsunaga1,2, Tatsuya Saitoh3,4, Keisuke Tabata1, Hiroko Omori1, Takashi Satoh3,4, Naoki Kurotori1, Ikuko Maejima1, Kanae Shirahama-Noda1, Tohru Ichimura5, Toshiaki Isobe5, Shizuo Akira3,4, Takeshi Noda1 & Tamotsu Yoshimori1,6
Abstract
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.
- Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1Yamadaoka, Suita, Osaka 565-0871, Japan.
- Department of Genetics, The Graduate University for Advanced Studies, Mishima 455-8540, Japan.
- Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1Yamadaoka, Suita, Osaka 565-0871, Japan.
- Department of Host Defense, Research Institute for Microbial Diseases. Osaka University, 3-1Yamadaoka, Suita, Osaka 565-0871, Japan.
- Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan.
- CREST, Japan Science and Technology Agency, Kawaguchi-Saitama 332-0012, Japan.
Correspondence to: Tamotsu Yoshimori1,6 e-mail: tamyoshi@biken.osaka-u.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
UVRAG reveals its second natureNature Cell Biology News and Views (01 Jul 2008)
Shaping membranes into autophagosomesNature Cell Biology News and Views (01 Oct 2007)
See all 4 matches for News And ViewsRESEARCH
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesisNature Cell Biology Article (01 Oct 2007)
Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1?phosphatidylinositol-3-kinase complexNature Cell Biology Letter (01 Apr 2009)
See all 28 matches for Research
