期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 17, 页码 13919-13929出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.348375
关键词
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资金
- Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- National Institute of Biomedical Innovation
- Takeda Science Foundation
- Uehara Memorial Foundation
- Sumitomo Foundation
- Naito Foundation
- Grants-in-Aid for Scientific Research [22019011, 23657084, 22570180, 22020009, 22770054, 22121505, 24121708, 22229002] Funding Source: KAKEN
Efficient apoptotic cell engulfment is important for both tissue homeostasis and immune response in mammals. In the present study, we report that Beclin 1 (a regulator of autophagy) is required for apoptotic cell engulfment. The engulfment process was largely abolished in Beclin 1 knock-out cells, and Beclin 1 knockdown significantly decreased apoptotic cell internalization in macrophage and fibroblast cell lines. Beclin 1 was recruited to the early phagocytic cup along with the generation of phosphatidylinositol 3-phosphate and Rac1, which regulates actin dynamics in lamellipodia. No lamellipodia were formed in Beclin 1 knock-out cells, and Beclin 1 knockdown completely inhibited the promotion of engulfment by ectopic expression of Rac1. Beclin 1 was co-immunoprecipitated with Rac1. These data indicate that Beclin 1 coordinates actin dynamics and membrane phospholipid synthesis to promote efficient apoptotic cell engulfment.
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