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Pubmed ID :23954414
Publication Date : //

Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.


The molecular mechanism of autophagy and its relationship to other lysosomal degradation pathways remain incompletely understood. Here, we identified a previously uncharacterized mammalian-specific protein, Beclin 2, which, like Beclin 1, functions in autophagy and interacts with class III PI3K complex components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced endolysosomal degradation of several G protein-coupled receptors (GPCRs) through its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased embryonic viability, and heterozygous knockout mice have defective autophagy, increased levels of brain cannabinoid 1 receptor, elevated food intake, and obesity and insulin resistance. Our findings identify Beclin 2 as a converging regulator of autophagy and GPCR turnover and highlight the functional and mechanistic diversity of Beclin family members in autophagy, endolysosomal trafficking, and metabolism.

Authors : He Congcong , Wei Yongjie , Sun Kai , Li Binghua , Dong Xiaonan , Zou Zhongju , Liu Yang , Kinch Lisa N , Khan Shaheen , Sinha Sangita , Xavier Ramnik J , Grishin Nick V , Xiao Guanghua , Eskelinen Eeva-Liisa , Scherer Philipp E , Whistler Jennifer L , Levine Beth ,

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