Toxic apoptosis

In This Issue In This Issue Toxic apoptosis antel et al. report that ␣-toxin from Staphylococcus aureus can induce apoptosis in immune cells (page 637). This may help the bacterium to immunosuppress the victim and continue proliferating. S. aureus was known to induce apoptosis, but the underlying mechanism was unknown. Bantel et al. find that the inducer is soluble. B Apoptosis can be triggered by a bacterial ␣-toxin. Experiments with antibodies and purified proteins indicate that the relevant soluble factor is ␣-toxin, which forms pores in the target cell membrane. The ␣-toxin activates intracellular caspases independently of transmembrane death receptor proteins, and can induce release of cytochrome c from isolated mitochondria. In both cases, however, the mechanism is likely to be indirect. Pores formed by ␣-toxin are unlikely to be big enough to allow either entry of ␣-toxin into the cell or exit of cytochrome c from mitochondria. Thus, apoptosis may be triggered by loss of monovalent ions through the plasma membrane pores. In addition, if the bacterium gains access to the inside of the cell, the intracellular ␣-toxin may form pores in mitochondria that activate a process leading to cytochrome c release. ᭿ Battle of the actin junctions homas Stossel is a fervent promoter of his favorite molecule, filamin. " For 25 years I've being saying that this protein is important for making orthogonal actin networks at the leading edge of the cell, " he says. " However, recent work has focused attention on a similar structural role for the Arp2/3 complex, which can nucleate actin filaments to form branched structures. " Stossel claims that branching is not sufficient for the formation of a strong actin network capable of pushing out the front of a migrating cell. A highly branched structure can still give way, like a bush that cannot support any significant weight. The cell needs to cross-link the branches together so that they no longer bend under pressure. This, says Stossel, is where filamin comes into the picture. On page 511, Stossel and colleagues take a closer look at actin filament structure in cells lacking filamin. These cells cannot migrate, and the authors find that they have a dense mat of actin filaments that are almost parallel to each other. The addition of filamin to these cells results in a more open, delicate, and three-dimensional actin network. By immunogold microscopy, many junctions between actin filaments contain filamin, …