Fig. 2. Cartoon illustrating the steps involved in activation of the cellular hypertonic stress response. In animal cells, the signals by which osmotic stress is detected and the signaling pathways, including inhibitory inputs, that regulate activation of regulatory volume increase (RVI) mechanisms, organic osmolyte accumulation and damage repair are poorly understood. Genome-wide RNAi screening in C. elegans suggests that disruption of new protein synthesis and cotranslational protein folding is one signal that activates organic osmolyte accumulation (see Fig. 4) (see also Lamitina et al., 2006).