TY - JOUR
T1 - XBeclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism
AU - He, Congcong
AU - Wei, Yongjie
AU - Sun, Kai
AU - Li, Binghua
AU - Dong, Xiaonan
AU - Zou, Zhongju
AU - Liu, Yang
AU - Kinch, Lisa N.
AU - Khan, Shaheen
AU - Sinha, Sangita
AU - Xavier, Ramnik J.
AU - Grishin, Nick V.
AU - Xiao, Guanghua
AU - Eskelinen, Eeva Liisa
AU - Scherer, Philipp E.
AU - Whistler, Jennifer L.
AU - Levine, Beth
N1 - Funding Information:
We thank Haley Harrington for assistance with manuscript preparation and the Electron Microscopy Unit of the Institute of Biotechnology, University of Helsinki, Finland for providing laboratory facilities. This work was supported by NIH awards ROI CA109618 (B.L.), ROI GM094575 (N.V.G.), ROI DK55758 (P.E.S.), PO1 DK088761 (P.E.S.), ROI DA019958 (J.L.W.), ROI DK043351 (R.J.X.), K99 DK094980 (C.H.), R21 AI078198 (S.S.), and P20 RR015566 (S.S.); a Welch Foundation Award I-1505 (N.V.G.); and funds provided by the state of California for medical research on alcohol and substance abuse through the University of California, San Francisco to J.L.W. E.-L.E. was supported by the Academy of Finland. The authors Y.W., K.S., and B. Li all contributed equally to this manuscript.
PY - 2013/8/29
Y1 - 2013/8/29
N2 - 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.
AB - 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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U2 - 10.1016/j.cell.2013.07.035
DO - 10.1016/j.cell.2013.07.035
M3 - Article
C2 - 23954414
AN - SCOPUS:84883464875
SN - 0092-8674
VL - 154
SP - X1085-1099
JO - Cell
JF - Cell
IS - 5
ER -