Insulation of Signaling Pathways Odor Discrimination via Olfactosomes?

The expression of these receptors in chemosensory neu-rons, along with the large size of the family, prompted the proposal that they might represent a new family of odorant receptors. Isolation of mutants defective in one of the C. elegans GCs allows functional testing of this proposal. In this regard, L'Etoile and Bargmann show that a truncated version of ODR-1 lacking the extracellu-lar domain of ODR-1 functions almost as well as the via Olfactosomes? wild-type product, which supports a role for ODR-1 downstream in olfactory signaling, rather than a role as an odorant receptor. Further experiments showed that the cyclase domain is required for olfactory signaling. An intriguing problem in neurobiology concerns the reg-This result is consistent with a requirement for cGMP ulation of signal integration versus signal insulation production and is of interest because all AWC-sensed within an individual neuron. In some cases signaling odorants are believed to act through a cGMP-sensitive pathways within a cell converge and integrate to gener-cation channel. ODR-1 was also shown, using GFP fu-ate a common unified output. In other cases, where a sion constructs, to be expressed in AWC and a small single neuron must be able to keep track of multiple number of other chemosensory neurons (although dif-independent signaling cascades, insulation to prevent ferent constructs containing different extents of flanking " cross-talk " between the pathways becomes critically DNA showed somewhat different expression patterns, important. The mechanisms of pathway insulation are providing a healthy reminder that such experiments re-particularly interesting in cases in which the insulated quire caution in interpretation). pathways share many common molecular components. L'Etoile and Bargmann then show a link between An excellent system in which to address the issue of ODR-1 and adaptation. When ODR-1 was overexpressed signal pathway insulation is the olfactory system of the by introducing high-copy transgenes of the wild-type nematode Caenorhabditis elegans. The worm is faced genomic clone into odr-1 mutant animals, a provocative with a daunting signal-to-noise problem: it must be able result was obtained: these ODR-1(OE) animals no longer to chemotax toward an odor source—a bacterial meal— adapted normally to butanone, although adaptation to through the rich odorous background of the soil in which benzaldehyde or isoamyl alcohol was normal. The same it lives. Moreover, it must accomplish this feat with a results were obtained when a cyclase-defective gene vanishingly small number of olfactory receptor neurons. was overexpressed, showing that this odor-specific ef-In …