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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1085-1099 |
| Number of pages | 15 |
| Journal | Cell |
| Volume | 154 |
| Issue number | 5 |
| DOIs | |
| State | Published - Aug 29 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. / He, Congcong; Wei, Yongjie; Sun, Kai; Li, Binghua; Dong, Xiaonan; Zou, Zhongju; Liu, Yang; Kinch, Lisa N.; Khan, Shaheen; Sinha, Sangita; Xavier, Ramnik J.; Grishin, Nick V.; Xiao, Guanghua; Eskelinen, Eeva Liisa; Scherer, Philipp E.; Whistler, Jennifer; Levine, Beth.
In: Cell, Vol. 154, No. 5, 29.08.2013, p. 1085-1099.Research output: Contribution to journal › Article
}
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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UR - http://www.scopus.com/inward/citedby.url?scp=84883464875&partnerID=8YFLogxK
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 -