title: Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages.
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.
authors.affiliation: Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tabata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Omori
authors.forename: Takashi
authors.initials: T
authors.lastname: Satoh
authors.forename: Naoki
authors.initials: N
authors.lastname: Kurotori
authors.forename: Ikuko
authors.initials: I
authors.lastname: Maejima
authors.forename: Kanae
authors.initials: K
authors.lastname: Shirahama-Noda
authors.forename: Tohru
authors.initials: T
authors.lastname: Ichimura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Isobe
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D045744:Cell Line, Tumor; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010588:Phagosomes / Q000648:ultrastructure; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins