The Ras-MAPK pathway is important for olfaction in Caenorhabditis elegans

The Ras-MAPK (mitogen-activated protein kinase) signal transduction pathway is well known to control cellular proliferation and differentiation in res ponse to extracellular signals, but its other functions are less understood . In Caenorhabditis elegans this pathway regulates several developmental ev ents, such as vulval induction and progression of meiosis(1), but its funct ion in the nervous system is unknown. Here we report that the Ras-MAPK path way is involved in olfaction in this organism. Mutational inactivation and hyperactivation of this pathway impairs efficiency of chemotaxis to a set o f odorants. Experiments in which let-60 ras was expressed using a heat-shoc k promoter and a cell-specific promoter show that a normal activity of LET- 60 Ras is required in mature olfactory neurons. Application of the odorant isoamylalcohol to wild-type animals leads to the activation of MAP kinase i n olfactory neurons within 10 seconds. This induction is dependent on the f unction of the nucleotide-gated channel TAX-2/TAX-4 and the voltage-activat ed calcium channel subunit UNC-2. These results suggest a dynamic regulator y role for the Ras-MAPK pathway in perception and transmission of sensory s ignals in olfactory neurons.