Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments.
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.
Solomon
Aharon
A
Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
Bandhakavi
Sricharan
S
Jabbar
Sean
S
Shah
Rena
R
Beitel
Greg J
GJ
Morimoto
Richard I
RI
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D003001:Cloning, Molecular; D015536:Down-Regulation; D004843:Epistasis, Genetic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009995:Osmosis; D010641:Phenotype; D020161:Physical Chromosome Mapping; D034622:RNA Interference; D015398:Signal Transduction; D013312:Stress, Physiological; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C495117:OSR-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases