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  Bim and Bmf Synergize To Induce Apoptosis in Neisseria Gonorrhoeae Infection

Kepp, O., Gottschalk, K., Churin, Y., Rajalingam, K., Brinkmann, V., Machuy, N., et al. (2009). Bim and Bmf Synergize To Induce Apoptosis in Neisseria Gonorrhoeae Infection. PLoS Pathogens, 5(3): e1000348.

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PLoS_Pathogens_2009_5_e1000348.pdf (Publisher version), 2MB
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© 2009 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.
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 Creators:
Kepp, Oliver1, Author              
Gottschalk, Kathleen1, Author              
Churin, Yuri1, Author              
Rajalingam, Krishnaraj1, Author              
Brinkmann, Volker2, Author              
Machuy, Nikolaus1, Author              
Kroemer, Guido, Author
Rudel, Thomas1, Author              
Affiliations:
1Department of Molecular Biology, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664147              
2Core Facilities / Microscopy, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664142              

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Free keywords: MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; INDUCED CELL-DEATH;; FACTOR-KAPPA-B; EPITHELIAL-CELLS; BCL-2 FAMILY; INFLAMMATORY CYTOKINES;; DEPENDENT APOPTOSIS; ACTIVATOR PROTEIN-1; MOTOR COMPLEX; BAX
 Abstract: 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-X-L, 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.

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Language(s): eng - English
 Dates: 2009-03
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 439759
ISI: 000266216000027
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Title: PLoS Pathogens
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Pages: - Volume / Issue: 5 (3) Sequence Number: e1000348 Start / End Page: - Identifier: ISSN: 1553-7366 %R e1000348 10.1371/journal.ppat.1000348