Caenorhabditis elegans OSR-1 Regulates Behavioral and Physiological Responses to Hyperosmotic Environments

Abstract

The molecular mechanisms that enable multicellular organisms to sense and modulate their responses to hyperosmotic environments are poorly understood. Here, we employ Caenorhabditis elegans to characterize the response of a multicellular organism to osmotic stress and establish a genetic screen to isolate mutants that are osmotic stress resistant (OSR). In this study, we describe the cloning of a novel gene, osr-1, and demonstrate that it regulates osmosensation, adaptation, and survival in hyperosmotic environments. Whereas wild-type animals exposed to hyperosmotic conditions rapidly lose body volume, motility, and viability, osr-1(rm1) mutant animals maintain normal body volume, motility, and viability even upon chronic exposures to high osmolarity environments. In addition, osr-1(rm1) animals are specifically resistant to osmotic stress and are distinct from previously characterized osmotic avoidance defective (OSM) and general stress resistance age-1(hx546) mutants. OSR-1 is expressed in the hypodermis and intestine, and expression of OSR-1 in hypodermal cells rescues the osr-1(rm1) phenotypes. Genetic epistasis analysis indicates that OSR-1 regulates survival under osmotic stress via CaMKII and a conserved p38 MAP kinase signaling cascade and regulates osmotic avoidance and resistance to acute dehydration likely by distinct mechanisms. We suggest that OSR-1 plays a central role in integrating stress detection and adaptation responses by invoking multiple signaling pathways to promote survival under hyperosmotic environments.

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

“…Similar to osm-8, osr-1 expression from the hypodermis, but not other cells, is sufficient to rescue osmotic phenotypes, suggesting a role in the cuticle or as a systemic signal (107) (Fig. 1F).…”

“…Remarkably, over 90% of individual C. elegans can survive direct transfer from 51 up to 400 mM NaCl (17)(18)(19)107). Approximate timing of physiological changes that occur following direct transfer to extreme hypertonicity is shown in Fig.…”

“…Mutant strains for three of these genes (osr-1, osm-7, and osm-11) have been characterized, and all three were confirmed to cause constitutive accumulation of glycerol (107,118). A later study characterized another gene encoding a predicted secreted protein, osm-8, as also functioning to suppress gpdh-1 expression and glycerol accumulation (100).…”

“…All four of these genes are expressed in the hypodermis, although in some cases not exclusively (57,100,107), suggesting that they could function with, or downstream from, the cuticle (Fig. 1C).…”

Insulin-like signaling pathway functions in integrative response to an olfactory and a gustatory stimuli in Caenorhabditis elegans

“…1C, all loss-of-function mutants of the positive regulators of the insulin pathway display higher proportions of (daf-2, akt-1/2 and sgk-1) crossing the Cu 2+ barrier, in contrast to the lower proportions in the daf-16 and daf-18 (negative regulators), and pdk-1 gain-of-function mutants. One exception was age-1(hx546) (Solomon et al, 2004), which was reluctant to cross the barrier. This seemingly contradicts the positive role of age-1 in insulin signaling; however, as we validated further (Fig.…”