title: 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.
authors.affiliation: Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Aharon
authors.initials: A
authors.lastname: Solomon
authors.forename: Sricharan
authors.initials: S
authors.lastname: Bandhakavi
authors.forename: Sean
authors.initials: S
authors.lastname: Jabbar
authors.forename: Rena
authors.initials: R
authors.lastname: Shah
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Beitel
authors.forename: Richard I
authors.initials: RI
authors.lastname: Morimoto
mesh_terms: 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
chemical_list: D029742:Caenorhabditis elegans Proteins; C495117:OSR-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases