Abstract
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.
Highlights
In order to effectively shape behavior, neural circuits must integrate sensory information by collating input and placing this input in a context of previous or concurrent sensory information
We found that reductions in cyclic guanosine monophosphate (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
We examined the localization of GFP::EGL-4 in daf-11 and odr-1 mutants
Summary
In order to effectively shape behavior, neural circuits must integrate sensory information by collating input and placing this input in a context of previous or concurrent sensory information. Chemosensation in AWC is mediated by the proposed direct binding of odor to seven transmembrane G-protein coupled receptors, which are exclusively localized to the sensory cilia [8,9]. These receptors are coupled to heterotrimeric Gproteins, whose a subunit can positively or negatively regulate odortaxis [10]. It is possible that odor decreases cGMP levels which favor closing of the cGMPgated channels and hyperpolarization of the AWC neuron This schema of acute odor binding in AWC shares many similarities with the light response in photoreceptor cells where in the absence of light calcium channels are open exhibiting a ‘dark current’. Upon binding of photons of light, a cGMP phosphodiesterase is activated which reduces cGMP levels causing closure of cyclic nucleotide gated channels, and hyperpolarizing the cell [18,19]
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