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Channels (Austin). 2014;8(1):76-83. doi: 10.4161/chan.26526. Epub 2013 Oct 2.

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

Author information

1
Medical Biochemistry and Molecular Biology; Saarland University; Homburg, Germany.
2
Experimental and Clinical Pharmacology and Toxicology; Saarland University; Homburg, Germany.

Abstract

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.

KEYWORDS:

ER calcium leakage; Pseudomonas aeruginosa Exotoxin A; Sec61 complex; calcium homeostasis; endoplasmic reticulum

PMID:
24088629
PMCID:
PMC4048345
DOI:
10.4161/chan.26526
[Indexed for MEDLINE]
Free PMC Article
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