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Cell Rep. 2015 Nov 17;13(7):1407-1417. doi: 10.1016/j.celrep.2015.10.011. Epub 2015 Nov 5.

RACK1 Promotes Autophagy by Enhancing the Atg14L-Beclin 1-Vps34-Vps15 Complex Formation upon Phosphorylation by AMPK.

Author information

1
Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PRC; Key Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475001, PRC.
2
Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PRC.
3
Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing 100083, PRC.
4
Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PRC.
5
Key Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan 475001, PRC.
6
Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PRC. Electronic address: zhangjy@nic.bmi.ac.cn.

Abstract

Autophagy is essential for maintaining tissue homeostasis. Although adaptors have been demonstrated to facilitate the assembly of the Atg14L-Beclin 1-Vps34-Vps15 complex, which functions in autophagosome formation, it remains unknown whether the autophagy machinery actively recruits such adaptors. WD40-repeat proteins are a large, highly conserved family of adaptors implicated in various cellular activities. However, the role of WD40-repeat-only proteins, such as RACK1, in postnatal mammalian physiology remains unknown. Here, we report that hepatocyte-specific RACK1 deficiency leads to lipid accumulation in the liver, accompanied by impaired Atg14L-linked Vps34 activity and autophagy. Further exploration indicates that RACK1 participates in the formation of autophagosome biogenesis complex upon its phosphorylation by AMPK at Thr50. Thr50 phosphorylation of RACK1 enhances its direct binding to Vps15, Atg14L, and Beclin 1, thereby promoting the assembly of the autophagy-initiation complex. These observations provide insight into autophagy induction and establish a pivotal role for RACK1 in postnatal mammalian physiology.

PMID:
26549445
DOI:
10.1016/j.celrep.2015.10.011
[Indexed for MEDLINE]
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