Bim and Bmf Synergize To Induce Apoptosis in Neisseria Gonorrhoeae Infection

PLoS Pathogens

Volker Brinkmann¹  Yuri Churin²  Nikolaus Machuy²  Kathleen Gottschalk²  Krishnaraj Rajalingam²  Oliver Kepp²  Thomas Rudel²  Guido Kroemer³ 

[1] Core Facility for Microscopy, Max Planck Institute for Infection Biology, Berlin, Germany;Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany;INSERM, U848, Institute Gustave Roussy, Université Paris Sud, Paris, France

关键词: Apoptosis;    Cytoskeleton;    HeLa cells;    Immunoprecipitation;    Antibodies;    Small interfering RNAs;    Host cells;    Neisseria gonorrhoeae;   

DOI  :  10.1371/journal.ppat.1000348

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY