title: Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation.
abstract: To navigate a complex and changing environment, an animal's sensory neurons must continually adapt to persistent cues while remaining responsive to novel stimuli. Long-term exposure to an inherently attractive odor causes Caenorhabditis elegans to ignore that odor, a process termed odor adaptation. Odor adaptation is likely to begin within the sensory neuron, because it requires factors that act within these cells at the time of odor exposure. The process by which an olfactory sensory neuron makes a decisive shift over time from a receptive state to a lasting unresponsive one remains obscure. In C. elegans, adaptation to odors sensed by the AWC pair of olfactory neurons requires the cGMP-dependent protein kinase EGL-4. Using a fully functional, GFP-tagged EGL-4, we show here that prolonged odor exposure sends EGL-4 into the nucleus of the stimulated AWC neuron. This odor-induced nuclear translocation correlates temporally with the stable dampening of chemotaxis that is indicative of long-term adaptation. Long-term adaptation requires cGMP binding residues as well as an active EGL-4 kinase. We show here that EGL-4 nuclear accumulation is both necessary and sufficient to induce long-lasting odor adaptation. After it is in the AWC nucleus, EGL-4 decreases the animal's responsiveness to AWC-sensed odors by acting downstream of the primary sensory transduction. Thus, the EGL-4 protein kinase acts as a sensor that integrates odor signaling over time, and its nuclear translocation is an instructive switch that allows the animal to ignore persistent odors.
authors.affiliation: Center for Neuroscience, University of California, Davis, CA 95618, USA.
authors.forename: Jin I
authors.initials: JI
authors.lastname: Lee
authors.forename: Damien M
authors.initials: DM
authors.lastname: O'Halloran
authors.forename: Jeffery
authors.initials: J
authors.lastname: Eastham-Anderson
authors.forename: Bi-Tzen
authors.initials: BT
authors.lastname: Juang
authors.forename: Julia A
authors.initials: JA
authors.lastname: Kaye
authors.forename: O
authors.initials: O
authors.lastname: Scott Hamilton
authors.forename: Bluma
authors.initials: B
authors.lastname: Lesch
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
authors.forename: Noelle D
authors.initials: ND
authors.lastname: L'Etoile
mesh_terms: D021581:Active Transport, Cell Nucleus; D000222:Adaptation, Physiological; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D017238:Genes, Helminth; D008959:Models, Neurological; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000502:physiology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012903:Smell / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D011993:Recombinant Fusion Proteins; D017869:Cyclic GMP-Dependent Protein Kinases; C470349:EGL-4 protein, C elegans; D006152:Cyclic GMP