Targeted cell killing by reconstituted caspases.

We have developed a two-component system involving reconstituted caspase (recCaspase) for selective and/or conditional ablation of targeted cells. Caspases, the executioners of programmed cell death, are normally synthesized as inactive zymogens and are activated by proteolytic processing of their subunits. We show here, using two different caspases, Caenorhabditis elegans CED-3 and human Caspase-3, that coexpression of the subunits generates constitutively active caspase activity that leads to cell death.

The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.

Mechanosensory transduction in touch receptor neurons is believed to be mediated by DEG/ENaC (degenerin/epithelial Na+ channel) proteins in nematodes and mammals. In the nematode Caenorhabditis elegans, gain-of-function mutations in the degenerin genes mec-4 and mec-10 (denoted mec-4(d) and mec-10(d), respectively) cause degeneration of the touch cells. This phenotype is completely suppressed by mutation in a third gene, mec-6 (refs 3, 4), that is needed for touch sensitivity.

MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation.

Touch sensitivity in animals relies on nerve endings in the skin that convert mechanical force into electrical signals. In the nematode Caenorhabditis elegans, gentle touch to the body wall is sensed by six mechanosensory neurons that express two amiloride-sensitive Na+ channel proteins (DEG/ENaC). These proteins, MEC-4 and MEC-10, are required for touch sensation and can mutate to cause neuronal degeneration.