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

Congcong He, Yongjie Wei, Kai Sun, Binghua Li, Xiaonan Dong, Zhongju Zou, Yang Liu, Lisa N. Kinch, Shaheen Khan, Sangita Sinha, Ramnik J. Xavier, Nick V. Grishin, Guanghua Xiao, Eeva Liisa Eskelinen, Philipp E. Scherer, Jennifer L. Whistler, Beth Levine

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84 Scopus citations

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 languageEnglish (US)
Pages (from-to)1085-1099
Number of pages15
JournalCell
Volume154
Issue number5
DOIs
StatePublished - Aug 29 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

He, C., Wei, Y., Sun, K., Li, B., Dong, X., Zou, Z., Liu, Y., Kinch, L. N., Khan, S., Sinha, S., Xavier, R. J., Grishin, N. V., Xiao, G., Eskelinen, E. L., Scherer, P. E., Whistler, J. L., & Levine, B. (2013). Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism. Cell, 154(5), 1085-1099. https://doi.org/10.1016/j.cell.2013.07.035