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PNAS 107 (13): 6016-6021

Copyright © 2010 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / NEUROSCIENCE

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

Jin I. Leea,1,2, Damien M. O'Hallorana,1, Jeffery Eastham-Andersona,3, Bi-Tzen Juanga, Julia A. Kayea,4, O. Scott Hamiltona, Bluma Leschb, Andrei Gogac, and Noelle D. L'Etoilea,d,5

aCenter for Neuroscience, University of California, Davis, CA 95618; bHoward Hughes Medical Institute, Laboratory of Neural Circuits and Behavior, Rockefeller University, New York, NY 10065; cDepartment of Medicine, University of California, San Francisco, CA 94143; and dDepartment of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA 95817

Communicated by Cornelia Bargmann, Rockefeller University, New York, NY, February 10, 2010 (received for review July 9, 2009)

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.

Key Words: neuron • plasticity • signaling • memory • integration


Freely available online through the PNAS open access option.

Author contributions: J.I.L., D.M.O., J.E.-A., A.G., and N.D.L. designed research; J.I.L., D.M.O., J.E.-A., B.-T.J., J.A.K., O.S.H., B.L., and N.D.L. performed research; J.I.L., D.M.O., J.E.-A., B.-T.J., J.A.K., B.L., A.G., and N.D.L. contributed new reagents/analytic tools; J.I.L., D.M.O., J.A.K., O.S.H., and N.D.L. analyzed data; and J.I.L., D.M.O., A.G., and N.D.L. wrote the paper.

1J.I.L. and D.M.O. contributed equally to this work.

2Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024.

3Present address: Department of Pathology, Genentech Inc., South San Francisco, CA 94080.

4Present address: Gladstone Institute of Neurological Disease, University of California, San Francisco, CA 94158.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/cgi/content/full/1000866107/DCSupplemental.

5To whom correspondence should be addressed. E-mail: ndletoile{at}ucdavis.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pan-Neuronal Expression of APL-1, an APP-Related Protein, Disrupts Olfactory, Gustatory, and Touch Plasticity in Caenorhabditis elegans.
C. Y. Ewald, R. Cheng, L. Tolen, V. Shah, A. Gillani, A. Nasrin, and C. Li (2012)
J. Neurosci. 32, 10156-10169
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Two Forms of Learning following Training to a Single Odorant in Caenorhabditis elegans AWC Neurons.
S. Pereira and D. van der Kooy (2012)
J. Neurosci. 32, 9035-9044
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