The Cyclic GMP-Dependent Protein Kinase EGL-4 Regulates Olfactory Adaptation in C. elegans

Abstract

Prolonged odor exposure causes a specific, reversible adaptation of olfactory responses. A genetic screen for negative regulators of olfaction uncovered mutations in the cGMP-dependent protein kinase EGL-4 that disrupt olfactory adaptation in C. elegans. G protein-coupled olfactory receptors within the AWC olfactory neuron signal through cGMP and a cGMP-gated channel. The cGMP-dependent kinase functions in AWC neurons during odor exposure to direct adaptation to AWC-sensed odors, suggesting that adaptation is a cell intrinsic process initiated by cGMP. A predicted phosphorylation site on the beta subunit of the cGMP-gated channel is required for adaptation after short odor exposure, suggesting that phosphorylation of signaling molecules generates adaptation at early time points. A predicted nuclear localization signal within EGL-4 is required for adaptation after longer odor exposure, suggesting that nuclear translocation of EGL-4 triggers late forms of adaptation.

Generation and modulation of chemosensory behaviors in C. elegans

“…In the background of a high constant concentration of one chemical, animals fail to respond to a point source of that chemical, but continue to respond to other chemicals sensed by that neuron type [71]. Similarly, prolonged exposure to one odorant decreases the response to that odorant while sparing responses to other chemicals sensed by that neuron [142,[145][146][147]. These observations indicate that the chemosensory system is able to discriminate among chemicals sensed by one neuron type.…”

“…Chemosensory responses are restored upon removal from the adapting chemical, with the time period of exposure correlating with the time required for recovery [146]. Early steps in adaptation may be mediated via modulation of activity of signaling components such as receptors, channels, and other signaling molecules via posttranslational mechanisms, resulting in cue-specific changes in sensory neuron responses [115,145,153,154] (Fig. 3a).…”

“…As mentioned above, prolonged exposure to high concentrations of a chemical results in worms failing to respond to a point source of the chemical. Adaptation appears to be biphasic with an early, rapid stage, and a later prolonged stage [145,146]. Chemosensory responses are restored upon removal from the adapting chemical, with the time period of exposure correlating with the time required for recovery [146].…”

“…3a). Thus, in the AWC olfactory neurons, phosphorylation of the TAX-2 channel appears to play an important role in the early adaptation stage [145], and this phosphorylation may be antagonized by the TAX-6 calcineurin phosphatase [155] (Fig. 3a).…”

“…However, later steps may require changes in gene expression. In the AWC neurons, cGMP-dependent protein kinase EGL-4 affects both early and late steps in adaptation, but interestingly, must be nuclear-translocated to effect the later stages [145] (N. L'Etoile, personal communication; Fig. 3a).…”