30th annual meeting 451.2

THE RAS/MAP KINASE PATHWAY IS INVOLVED IN OLFACTION IN CAENORHABDITIS ELEGANS.
T. Hirotsu, S. Saeki and Y. Iino.
Mol. Genet. Res. Lab., Univ. of Tokyo, Tokyo 113-0033.

In C. elegans, the Ras-MAPK signal transduction pathway is known to play roles in vulval induction and several other developmental events, but the function of the pathway in the nervous system is unknown. Here we report that the Ras-MAPK pathway is involved in olfaction in this organism.

Chemotaxis to volatile odorants is mediated by two pairs of chemosensory neurons : AWA and AWC. Mutants affected in the Ras-MAPK pathway showed defects in chemotaxis to AWA- and AWC-sensed odorants. The expression of let-60 ras in adults mimicked the defects in mutants, but the expression during embryogenesis did not. Further, the AWC-specific expression of ras altered chemotactic response to isoamylalcohol (which is sensed by AWC), but not to diacetyl (sensed by AWA). These results suggest that the normal activity of LET-60 Ras is required in mature AWC neurons.

To determine how the Ras-MAPK pathway is activated in olfactory neurons, we observed accumulation of activated MAPK by immunofluorescence. The activation of MAPK in the AWC neurons was detected after 10 seconds of application of isoamylalcohol. Axons, dendrites and cell bodies were stained, whereas no staining was shown in the sensory cilia. This activation was dependent on the function of the cyclic-nucleotide gated channel TAX-2/TAX-4 and the voltage-activated calcium channel subunit UNC-2. We propose that the Ras-MAPK pathway plays a regulatory role in perception and transmission of sensory signals downstream of these ion channels in olfactory neurons.