Involvement of Beclin 1 in engulfment of apoptotic cells

J Biol Chem. 2012 Apr 20;287(17):13919-29. doi: 10.1074/jbc.M112.348375. Epub 2012 Mar 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Autophagy
  • Beclin-1
  • Embryonic Stem Cells / cytology*
  • Gene Library
  • Humans
  • Image Processing, Computer-Assisted
  • Jurkat Cells
  • Membrane Proteins / metabolism*
  • Mice
  • Microscopy, Electron / methods
  • NIH 3T3 Cells
  • Neuropeptides / metabolism*
  • Phagocytosis
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plasmids / metabolism
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Becn1 protein, mouse
  • Membrane Proteins
  • Neuropeptides
  • RAC1 protein, human
  • Rac1 protein, mouse
  • Phosphatidylinositol 3-Kinases
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein