Beclin 2 Functions in Autophagy, Degradation of G Protein-Coupled Receptors, and Metabolism

نویسندگان

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

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.

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عنوان ژورنال:
  • Cell

دوره 154  شماره 

صفحات  -

تاریخ انتشار 2013