Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation

Jin I. Lee, Damien M. O'Halloran, Jeffery Eastham-Anderson, Bi-Tzen Juang, Julia A. Kaye, O. Scott Hamilton, Bluma Lesch, Andrei Goga, Noelle D. L'Etoile

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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 Caenor habditis 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.

Original languageEnglish
Pages (from-to)6016-6021
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - 30 Mar 2010


  • Integration
  • Memory
  • Neuron
  • Plasticity
  • Signaling

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