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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 response to extracellular signals, but its other functions are less understood. In Caenorhabditis elegans this pathway regulates several developmental events, such as vulval induction and progression of meiosis1, but its function in the nervous system is unknown. Here we report that the Ras-MAPK pathway is involved in olfaction in this organism. Mutational inactivation and hyperactivation of this pathway impairs efficiency of chemotaxis to a set of odorants. Experiments in which let-60 ras was expressed using a heat-shock 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 in olfactory neurons within 10 seconds. This induction is dependent on the function of the nucleotide-gated channel TAX-2/TAX-4 and the voltage-activated calcium channel subunit UNC-2. These results suggest a dynamic regulatory role for the Ras-MAPK pathway in perception and transmission of sensory signals in olfactory neurons.

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Figure 1: Chemotaxis of mutants affected in the Ras-MAPK pathway.
Figure 2: AWC neurons visualized with the gcy-10::GFP marker.
Figure 3: Temporally and spatially restricted expression of let-60 affects chemotaxis to odorants.
Figure 4: Activation of MAPK by odorant stimulus.


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We thank D. Garbers for the gcy-10::GFP reporter plasmid; M. Han for let-60 cDNAs and the mek-2(ku114) strain; M. Koga, Y. Ohshima, N. Hisamoto and K. Matsumoto for pEF1α::GFP; A. Fire for vectors; and C. Bargmann, T. Schedl and Y. Emori for their comments and advice. All other nematode strains used in this study were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR).

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Correspondence to Yuichi Iino.

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Hirotsu, T., Saeki, S., Yamamoto, M. et al. The Ras-MAPK pathway is important for olfaction in Caenorhabditis elegans. Nature 404, 289–293 (2000).

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