Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans
| Autor: | O. Scott Hamilton, Jin I. Lee, Noelle D. L'Etoile, Damien M. O'Halloran, Maria Gallegos |
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| Přispěvatelé: | Dupuy, Denis |
| Rok vydání: | 2012 |
| Předmět: |
IBMX
animal structures Sensory Receptor Cells General Science & Technology Active Transport Cell Nucleus lcsh:Medicine Biology Olfactory Receptor Neurons 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Model Organisms Molecular Cell Biology medicine Cyclic GMP-Dependent Protein Kinases Genetics Animals 2.1 Biological and endogenous factors Aetiology lcsh:Science Caenorhabditis elegans Caenorhabditis elegans Proteins Cyclic GMP 030304 developmental biology Cell Nucleus 0303 health sciences Multidisciplinary CGMP binding lcsh:R fungi Phosphodiesterase Animal Models Signaling in Selected Disciplines Olfactory fatigue Sensory Systems Active Transport Cell biology Cell nucleus medicine.anatomical_structure chemistry lcsh:Q Neuron cGMP-dependent protein kinase 030217 neurology & neurosurgery Nuclear localization sequence Research Article Signal Transduction Neuroscience |
| Zdroj: | PloS one, vol 7, iss 2 PLoS ONE PLoS ONE, Vol 7, Iss 2, p e31614 (2012) |
| Popis: | The Protein Kinase G, EGL-4, is required within the C. elegans AWC sensory neurons to promote olfactory adaptation. After prolonged stimulation of these neurons, EGL-4 translocates from the cytosol to the nuclei of the AWC. This nuclear translocation event is both necessary and sufficient for adaptation of the AWC neuron to odor. A cGMP binding motif within EGL-4 and the Gα protein ODR-3 are both required for this translocation event, while loss of the guanylyl cyclase ODR-1 was shown to result in constitutively nuclear localization of EGL-4. However, the molecular changes that are integrated over time to produce a stably adapted response in the AWC are unknown. Here we show that odor-induced fluctuations in cGMP levels in the adult cilia may be responsible in part for sending EGL-4 into the AWC nucleus to produce long-term adaptation. We found that reductions in cGMP that result from mutations in the genes encoding the cilia-localized guanylyl cyclases ODR-1 and DAF-11 result in constitutively nuclear EGL-4 even in naive animals. Conversely, increases in cGMP levels that result from mutations in cGMP phosphodiesterases block EGL-4 nuclear entry even after prolonged odor exposure. Expression of a single phosphodiesterase in adult, naive animals was sufficient to modestly increase the number of animals with nuclear EGL-4. Further, coincident acute treatment of animals with odor and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) decreased the number of animals with nuclear EGL-4. These data suggest that reducing cGMP levels in AWC is necessary and even partially sufficient for nuclear translocation of EGL-4 and adaptation as a result of prolonged odor exposure. Our genetic analysis and chemical treatment of C. elegans further indicate that cilia morphology, as defined by fluorescent microscopic observation of the sensory endings, may allow for odor-induced fluctuations in cGMP levels and this fluctuation may be responsible for sending EGL-4 into the AWC nucleus. |
| Databáze: | OpenAIRE |
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