Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages.
Journal:
Nat. Cell Biol. 2009 AprAuthors:
Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T
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
...[more]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.[less]
Mesh Headings:
Adaptor Proteins, Vesicular Transport, Animals, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Tumor, Endocytosis, Green Fluorescent Proteins, Humans, Membrane Proteins, Mice, Microtubule-Associated Proteins, Multiprotein Complexes, Phagosomes, Protein Binding, Protein Processing, Post-Translational, RNA, Small Interfering, Recombinant Fusion Proteins