title: Involvement of Beclin 1 in engulfment of apoptotic cells.
abstract: 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.
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. konishi.mtt@mri.tmd.ac.jp
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Konishi
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yue
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D053595:Embryonic Stem Cells / Q000166:cytology*; D015723:Gene Library; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron / Q000379:methods; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000378:metabolism*; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008565:Membrane Proteins; D009479:Neuropeptides; C107953:RAC1 protein, human; C484602:Rac1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein