Open AccessChannels formed by subnanomolar concentrations of the toxin aerolysin trigger apoptosis of T lymphomas
Author(s) -
Nelson Kim L.,
Brodsky Robert A.,
Buckley J. Thomas
Publication year - 1999
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1046/j.1462-5822.1999.00009.x
Subject(s) - aerolysin , apoptosis , biology , toxin , microbiology and biotechnology , receptor , intracellular , biochemistry , gene , virulence
Aerolysin is a channel‐forming toxin that binds to glycosylphosphatidylinositol (GPI)‐anchored proteins, such as Thy‐1, on target cells. Here, we show that subnanomolar concentrations of aerolysin trigger apoptosis of T lymphomas. Using inactive aerolysin variants, we determined that apoptosis was not directly triggered by binding to GPI‐anchored receptors, nor was it caused by receptor clustering induced by toxin oligomerization. Apoptosis was caused by the production of a small number of channels in the cell membrane. Channel formation resulted in a rapid increase in intracellular calcium, which may have been the signal for apoptosis. Overexpression of the antiapoptotic protein bcl‐2 blocked aerolysin‐induced apoptosis, although this effect was overcome at higher toxin concentrations.