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First published online April 20, 2007
Journal of Experimental Biology 210, 1622-1631 (2007)
Published by The Company of Biologists 2007
doi: 10.1242/jeb.000125

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Revisiting the Krogh Principle in the post-genome era: Caenorhabditis elegans as a model system for integrative physiology research

Kevin Strange

Departments of Anesthesiology, Molecular Physiology and Biophysics, and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA

View larger version (25K): [in this window] [in a new window]   Fig. 1. Cartoon illustrating the hypertonic stress response of animal cells. Exposure to hypertonic media causes rapid water loss and cell shrinkage. Cells respond to shrinkage by activating regulatory volume increase (RVI) salt uptake mechanisms. Osmotically obliged water follows salt uptake and cell volume returns to its original value. Over a period of several hours, cells replace inorganic ions accumulated during RVI with organic osmolytes. Accumulation of organic osmolytes is mediated either by energy-dependent transport from the external medium or by changes in the rates of osmolyte synthesis and degradation. Hypertonic stress typically increases the expression of both organic osmolyte transporters and key enzymes involved in their synthesis. Cells also repair molecular damage including DNA breaks and protein denaturation induced by the initial cell shrinkage and elevation cell inorganic ion levels.

View larger version (13K): [in this window] [in a new window]   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).

View larger version (11K): [in this window] [in a new window]   Fig. 3. Pie chart showing distribution of the functional categories of the 122 rgpd genes identified by genome-wide RNAi screening in C. elegans (Lamitina et al., 2006).

View larger version (21K): [in this window] [in a new window]   Fig. 4. Model for regulation of osmosensitive gene expression by disruption of protein homeostasis. Hypertonic stress induced water loss causes elevated cytoplasmic ionic strength, which in turn disrupts new protein synthesis and cotranslational protein folding (see Lamitina et al., 2006). Damaged proteins function as a signal that activates gpdh-1 expression and glycerol synthesis. Glycerol replaces inorganic ions in the cytoplasm and functions as a chemical chaperone that aids in the refolding of misfolded proteins. Loss of function of protein homeostasis genes also causes accumulation of damaged proteins and activation of gpdh-1 expression.