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PMID: 9889191 Published · ppublish English Journal Article

Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases.

The EMBO journal ·Vol. 18 ·No. 2 ·1999-01-15 ·Pages 339-52

Müller A, Günther D, Düx F, Naumann M, Meyer TF, Rudel T

Abstract

The porin (PorB) of Neisseria gonorrhoeae is an intriguing bacterial factor owing to its ability to translocate from the outer bacterial membrane into host cell membranes where it modulates the infection process. Here we report on the induction of programmed cell death after prolonged infection of epithelial cells with pathogenic Neisseria species. The underlying mechanism we propose includes translocation of the porin, a transient increase in cytosolic Ca2+ and subsequent activation of the Ca2+ dependent protease calpain as well as proteases of the caspase family. Blocking the porin channel by ATP eliminates the Ca2+ signal and also abolishes its pro-apoptotic function. The neisserial porins share structural and functional homologies with the mitochondrial voltage-dependent anion channels (VDAC). The neisserial porin may be an analogue or precursor of the ancient permeability transition pore, the putative central regulator of apoptosis.

MeSH Terms
Adenosine Triphosphate/pharmacology Amino Acid Chloromethyl Ketones/pharmacology Apoptosis/drug effects,physiology Bacterial Outer Membrane Proteins/genetics,metabolism,toxicity Calcium/metabolism Calpain/metabolism Cell Line Cysteine Endopeptidases/metabolism Cysteine Proteinase Inhibitors/pharmacology Enzyme Activation/drug effects HeLa Cells Humans Ion Transport/drug effects Mutation Neisseria gonorrhoeae/genetics,metabolism,pathogenicity Porins/genetics,metabolism,toxicity
Chemicals
Amino Acid Chloromethyl Ketones Bacterial Outer Membrane Proteins Cysteine Proteinase Inhibitors Porins benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone porin protein, Neisseria Adenosine Triphosphate Calpain Cysteine Endopeptidases Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Müller A
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Monbijoustrasse 2, 10117 Berlin, Germany.
Günther D
Düx F
Naumann M
Meyer T F
Rudel T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1999-01-15
Pages
339-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171129
Subset
IM
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