File:Cell apoptosis 01.mp4

Cytoskeletal changes prior to cell death

Cells were cultured in glass-bottom dishes and placed under an Olympus spinning disc microscope. Phase contrast pictures of the cells were taken every 10 min upon infection.

Reference

<pubmed>19300516</pubmed>PLoS Pathog.

Copyright

Kepp et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2654407&blobname=ppat.1000348.s012.avi

AVI relabeled converted to MP4 file 1.7 Mb

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection. Kepp O, Gottschalk K, Churin Y, Rajalingam K, Brinkmann V, Machuy N, Kroemer G, Rudel T. PLoS Pathog. 2009 Mar;5(3):e1000348. Epub 2009 Mar 20.

PMID 19300516

Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells.