Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases.
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.
Müller
A
A
Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Monbijoustrasse 2, 10117 Berlin, Germany.
Günther
D
D
Düx
F
F
Naumann
M
M
Meyer
T F
TF
Rudel
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D018272:Porins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity
D000590:Amino Acid Chloromethyl Ketones; D001425:Bacterial Outer Membrane Proteins; D015853:Cysteine Proteinase Inhibitors; D018272:Porins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C057699:porin protein, Neisseria; D000255:Adenosine Triphosphate; D002154:Calpain; D003546:Cysteine Endopeptidases; D002118:Calcium