4.6 Article

Involvement of Beclin 1 in Engulfment of Apoptotic Cells

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

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资金

  1. Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology
  2. Ministry of Education, Culture, Sports, Science and Technology of Japan
  3. National Institute of Biomedical Innovation
  4. Takeda Science Foundation
  5. Uehara Memorial Foundation
  6. Sumitomo Foundation
  7. Naito Foundation
  8. Grants-in-Aid for Scientific Research [22019011, 23657084, 22570180, 22020009, 22770054, 22121505, 24121708, 22229002] Funding Source: KAKEN

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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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