Serpins are a superfamily of lysosomal cysteine and/or serine proteinase inhibitors. We identified one member of the C. elegans serpin family,
srp-6, that inhibited the lysosomal cysteine proteinases. Srp-6 was expressed predominantly in the gland cell and the vulval muscles. The longevity and morphology of the
srp-6 knockout animals were normal. However the serpin knockout animal had an adverse response to hypoosmotic stress. Compared to N2 worms,
srp-6 -/- animals show a marked decreased in survivability when placed in water (98% vs 10% viability, respectfully). A phenocopy induced by RNAi in adult worms showed that this defect was not due to a developmental abnormality. Using genetic and pharmacological approaches, we showed that hypoosmotic death in
srp-6 -/- animals was associated with prolonged elevations in intracellular calcium and was independent of the classical apoptopic cell death pathway, but involves proteolysis by cysteine proteinases. We are now undertaking a genetic screen to determine other genes that may fall in this pathway. These data suggest that Srp-6 plays a role in protecting C. elegans from hypoosmotic shock.