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Interaction of Pseudomonas aeruginosa Exotoxin A with the human Sec61 complex suppresses passive calcium efflux from the endoplasmic reticulum

2013; Taylor & Francis; Volume: 8; Issue: 1 Linguagem: Inglês

10.4161/chan.26526

1933-6969

Nico Schäuble, Adolfo Cavalié, Richard Zimmermann, Martin Jung,

Clostridium difficile and Clostridium perfringens research

According to live-cell calcium-imaging experiments, the Sec61 complex is a passive calcium-leak channel in the human endoplasmic reticulum (ER) membrane that is regulated by ER luminal immunoglobulin heavy chain binding protein (BiP) and cytosolic Ca(2+)-calmodulin. In single channel measurements, the open Sec61 complex is Ca(2+) permeable. It can be closed not only by interaction with BiP or Ca(2+)-calmodulin, but also with Pseudomonas aeruginosa Exotoxin A which can enter human cells by retrograde transport. Exotoxin A has been shown to interact with the Sec61 complex and, thereby, inhibit ER export of immunogenic peptides into the cytosol. Here, we show that Exotoxin A also inhibits passive Ca(2+) leakage from the ER in human cells, and we characterized the N-terminus of the Sec61 α-subunit as the relevant binding site for Exotoxin A.