The Persistent Smell in the Nucleus

Science Signaling  13 Apr 2010:
Vol. 3, Issue 117, pp. ec110
DOI: 10.1126/scisignal.3117ec110

In the AWC sensory neurons of Caenorhabditis elegans, signaling cascades are activated upon detection of certain odors, such as benzaldehyde and butanone, to initiate attractive responses (such as chemotaxis) and adaptation. Short-term adaptation to an odor (on the order of 30 minutes) requires the cGMP-activated kinase EGL-4. Lee et al. found that EGL-4 was also necessary for long-term or persistent adaptation to an odor (on the order of 80 minutes). Eighty minutes of pre-exposure to benzaldehyde decreased the benzaldehyde chemotaxis index of wild-type animals but not that of animals lacking EGL-4. In animals expressing EGL-4 tagged with green fluorescent protein (GFP-EGL-4) in a subset of sensory neurons, the localization of GFP-EGL-4 in AWC neurons changed from largely cytoplasmic in the naïve state to nuclear after 80 minutes of benzaldehyde exposure. Nuclear accumulation of EGL-4 and persistent adaptation (as shown by unaltered benzaldehyde chemotaxis indices) were reduced in animals expressing forms of EGL-4 with mutations in the cGMP-binding or kinase domains. Furthermore, animals expressing an EGL-4 mutant lacking the nuclear localization signal did not show long-term adaptation to benzaldehyde, and expression of a constitutively nuclear EGL-4 decreased the response of naïve animals to benzaldehyde and other odors detected by AWC neurons. Persistent exposure to butanone causes a switch from attractive to repulsive responses in starving animals. EGL-4 was cytoplasmic in naïve animals not exposed to butanone but nuclear in most animals that were repulsed by butanone. Nuclear EGL-4 was required for the switch from attractive to repulsive responses to butanone, which suggests that nuclear EGL-4 modified responses that were initiated after primary odor sensation. Thus, nuclear translocation of EGL-4 is required for long-term odor adaptation in C. elegans.

J. I. Lee, D. M. O’Halloran, J. Eastham-Anderson, B.-T. Juang, J. A. Kaye, O. S. Hamilton, B. Lesch, A. Goga, N. D. L’Etoile, Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation. Proc. Natl. Acad. Sci. U.S.A. 107, 6016–6021 (2010). [Abstract] [Full Text]