title: Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.
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.
authors: 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.
authors: Congcong
authors: C
authors: He
authors: 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.
authors: Yongjie
authors: Y
authors: Wei
authors: 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.
authors: Kai
authors: K
authors: Sun
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Binghua
authors: B
authors: Li
authors: 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.
authors: Xiaonan
authors: X
authors: Dong
authors: 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.
authors: Zhongju
authors: Z
authors: Zou
authors: 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.
authors: Yang
authors: Y
authors: Liu
authors: 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.
authors: Lisa N
authors: LN
authors: Kinch
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Shaheen
authors: S
authors: Khan
authors: Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58102, USA.
authors: Sangita
authors: S
authors: Sinha
authors: 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.
authors: Ramnik J
authors: RJ
authors: Xavier
authors: 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.
authors: Nick V
authors: NV
authors: Grishin
authors: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Guanghua
authors: G
authors: Xiao
authors: Department of Biosciences, Division of Biochemistry and Biotechnology, University of Helsinki, Helsinki, FI-00014 Finland.
authors: Eeva-Liisa
authors: EL
authors: Eskelinen
authors: 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.
authors: Philipp E
authors: PE
authors: Scherer
authors: Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, CA 94608, USA.
authors: Jennifer L
authors: JL
authors: Whistler
authors: 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.
authors: Beth
authors: B
authors: Levine
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; C584110:BECN2 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C584111:Becn2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled
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