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

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

  • Cell. 2013 Aug 29;154(5):1085-1099. doi: 10.1016/j.cell.2013.07.035.
Congcong He 1,  Yongjie Wei 1,  Kai Sun 2,  Binghua Li 3,  Xiaonan Dong 4,  Zhongju Zou 1,  Yang Liu 4,  Lisa N Kinch 5,  Shaheen Khan 3,  Sangita Sinha 6,  Ramnik J Xavier 7,  Nick V Grishin 5,  Guanghua Xiao 8,  Eeva-Liisa Eskelinen 9,  Philipp E Scherer 2,  Jennifer L Whistler 10,  Beth Levine 11
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 2 Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 4 Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 6 Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58102, USA.
  • 7 Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • 8 Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 9 Department of Biosciences, Division of Biochemistry and Biotechnology, University of Helsinki, Helsinki, FI-00014 Finland.
  • 10 Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA.
  • 11 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: beth.levine@utsouthwestern.edu.
PMID: 23954414 DOI: 10.1016/j.cell.2013.07.035
Abstract

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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