The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans
Autor: | Isabel Beets, Matthew A. Churgin, Christopher Fang-Yen, Matthew D. Nelson, David M. Raizen, Lindsey E Lopes, Liliane Schoofs, Michael J Iannacone |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Nervous system medicine.medical_specialty Receptors Peptide QH301-705.5 Science Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine GPCR sickness Stress Physiological Internal medicine medicine Animals Biology (General) sleep Receptor Caenorhabditis elegans Caenorhabditis elegans Proteins General Immunology and Microbiology Mechanism (biology) General Neuroscience Stress induced Neuropeptides General Medicine Sleep in non-human animals 3. Good health RFamide On cells 030104 developmental biology medicine.anatomical_structure Endocrinology Gene Expression Regulation C. elegans Medicine Wakefulness Neuroscience 030217 neurology & neurosurgery Research Article |
Zdroj: | eLife eLife, Vol 6 (2017) |
ISSN: | 2050-084X |
Popis: | In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo, is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness. DOI: http://dx.doi.org/10.7554/eLife.19837.001 eLife digest People often feel fatigued and sleepy when they are sick. Other animals also show signs of sleepiness when ill – they stop eating, move less, and are less responsive to changes in their environment. Sickness-induced sleep helps both people and other animals to recover, and many scientists believe that this type of sleep is different than nightly sleep. Studies of sickness-induced sleep have made use of a simple worm with a simple nervous system. In this worm, a single nerve cell releases chemicals that cause the worm to fall asleep in response to illness. Animals exposed to one of these chemicals, called FLP-13, fall asleep even when they are not sick. As such, scientists would like to know which cells in the nervous system FLP-13 interacts with, what receptor the cells use to recognize this chemical, and whether it turns on cells that induce sleep or turns off the cells that cause wakefulness. Now, Iannacone et al. show that FLP-13 likely causes sleep by turning down activity in the cells in the nervous system that promote wakefulness. The experiments sifted through genetic mutations to determine which ones cause the worms not to fall asleep when FLP-13 is released. This revealed that worms with a mutation that causes them to lack a receptor protein called DMSR-1 do not become sleepy in response to FLP-13. This suggests that DMSR-1 must be essential for FLP-13 to trigger sleep. About 10% of cells in the worm’s nervous system have the DMSR-1 receptor. Some of these neurons tell the worm to move forward or to forage around for food. The experiments also showed that FLP-13 is probably not the only chemical that interacts with the DMSR-1 receptor, but the identities of these other chemicals remain unknown. Additional experiments are now needed to determine if sickness-induced sleepiness in humans and other mammals is triggered by a similar mechanism. If it is, then drugs might be developed to treat people experiencing fatigue associated with sickness as well as other unexplained cases of fatigue. DOI: http://dx.doi.org/10.7554/eLife.19837.002 |
Databáze: | OpenAIRE |
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