Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors

PLoS Pathogens

Laurence Abrami¹  F. Gisou van der Goot¹  Mirko Bischofberger¹  Béatrice Kunz¹  Romain Groux¹ 

[1] Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Faculty of Life Sciences, Lausanne, Switzerland

关键词: Toxins;    Actins;    Endocytosis;    HeLa cells;    Anthrax;    Small interfering RNAs;    Ubiquitination;    RNA interference;   

DOI  :  10.1371/journal.ppat.1000792

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The anthrax toxin is a tripartite toxin, where the two enzymatic subunits require the third subunit, the protective antigen (PA), to interact with cells and be escorted to their cytoplasmic targets. PA binds to cells via one of two receptors, TEM8 and CMG2. Interestingly, the toxin times and triggers its own endocytosis, in particular through the heptamerization of PA. Here we show that PA triggers the ubiquitination of its receptors in a β-arrestin-dependent manner and that this step is required for clathrin-mediated endocytosis. In addition, we find that endocytosis is dependent on the heterotetrameric adaptor AP-1 but not the more conventional AP-2. Finally, we show that endocytosis of PA is strongly dependent on actin. Unexpectedly, actin was also found to be essential for efficient heptamerization of PA, but only when bound to one of its 2 receptors, TEM8, due to the active organization of TEM8 into actin-dependent domains. Endocytic pathways are highly modular systems. Here we identify some of the key players that allow efficient heptamerization of PA and subsequent ubiquitin-dependent, clathrin-mediated endocytosis of the anthrax toxin.

【 授权许可】

CC BY