C. elegans Notch Signaling Regulates Adult Chemosensory Response and Larval Molting Quiescence

被引:97
作者
Singh, Komudi [1 ]
Chao, Michael Y. [2 ]
Somers, Gerard A. [3 ,4 ]
Komatsu, Hidetoshi [3 ,4 ]
Corkins, Mark E. [1 ]
Larkins-Ford, Jonah [3 ,4 ]
Tucey, Tim [3 ,4 ]
Dionne, Heather M. [3 ,4 ]
Walsh, Melissa B. [5 ]
Beaumont, Emma K. [1 ,6 ]
Hart, Douglas P. [7 ]
Lockery, Shawn R. [8 ]
Hart, Anne C. [1 ]
机构
[1] Brown Univ, Dept Neurosci, Providence, RI 02912 USA
[2] Calif State Univ San Bernardino, Dept Biol, San Bernardino, CA 92407 USA
[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA
[4] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA
[5] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA
[6] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England
[7] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[8] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA
基金
美国国家卫生研究院;
关键词
DEPENDENT PROTEIN-KINASE; GLR-1; GLUTAMATE-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; TERM-MEMORY FORMATION; CAENORHABDITIS-ELEGANS; SYNAPTIC PLASTICITY; GENE-EXPRESSION; DROSOPHILA; SLEEP; IDENTIFICATION;
D O I
10.1016/j.cub.2011.04.010
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: The conserved DOS-motif proteins OSM-7 and OSM-11 function as coligands with canonical DSL (Delta, Serrate, and LAG-2) ligands to activate C. elegans Notch receptors during development. We report here that Notch ligands, coligands, and the receptors LIN-12 and GLP-1 regulate two C. elegans behaviors: chemosensory avoidance of octanol and quiescence during molting lethargus. Results: C. elegans lacking osm-7 or osm-11 are defective in their response to octanol. We find that OSM-11 is secreted from hypodermal seam cells into the pseudocoelomic body cavity and acts non-cell autonomously as a diffusible factor. OSM-11 acts with the DSL ligand LAG-2 to activate LIN-12 and GLP-1 Notch receptors in the neurons of adult animals, thereby regulating octanol avoidance response. In adult animals, overexpression of osm-11 and consequent Notch receptor activation induces anachronistic sleep-like quiescence. Perturbation of Notch signaling alters basal activity in adults as well as arousal thresholds and quiescence during molting lethargus. Genetic epistasis studies reveal that Notch signaling regulates quiescence via previously identified circuits and genetic pathways including the egl-4 cGMP-dependent kinase. Conclusions: Our findings indicate that the conserved Notch pathway modulates behavior in adult C. elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans, suggesting that Notch may regulate sleep in other species.
引用
收藏
页码:825 / 834
页数:10
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