TY - JOUR
T1 - Beclin 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
AU - Levine, Beth
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
VL - 154
SP - 1085
EP - 1099
JO - Cell
JF - Cell
SN - 0092-8674
IS - 5
ER -