Calcineurin, calcium/calmodulin-dependent phosphatase, is involved in a variety of calcium signaling cascades. In the absence of calcium, the phosphatase activity of calcineurin A subunit is inhibited by its own autoinhibitory domain. In the presence of calcium, binding of calcium/calmodulion and calcineurin B subunit to the A subunit releases the autoinihibition and triggers the drastic increase of the catalytic activity. Despite the abundant expression of calcineurin in mammalian brain, its neuronal function is poorly understood. We found that
tax-6 gene encodes sole calcineurin A subunit in C. elegans and that its function is essential for the sensory systems. A reduction-of-function mutation,
tax-6(
p675) , was originally isolated as chemotaxis-defective mutant for NaCl (1) and was also found to show thermophilic (heat-seeking) phenotype in thermotaxis (2). TAX-6 calcineurin was mainly expressed in sensory neurons, such as thermosensory neuron AFD, chemosensory neuron ASE, AWA, AWC, and osmosensory neuron ASH. The specific expression of
tax-6 cDNA in AFD thermosensory neurons of
tax-6 mutants rescued AFD-mediated defective thermotaxis, but did not rescue ASE-mediated defective chemotaxis, indicating that
tax-6 functions cell-autonomously in AFD neurons. Interestingly, either killing AFD or expressing constitutively activated TAX-6 in AFD results in cryophilic and/or athermotactic phenotype. These results suggest that thermophilic phenotype exhibited by
tax-6 mutation is caused by hyper-activation of AFD neurons. Consistent with the hyper-activation of sensory neurons by the loss of TAX-6 function,
tax-6 mutants also showed hypersensitive osmotic avoidance mediated by the ASH neurons. To address how and where TAX-6 calcineurin functions in sensory signaling, we behaviorally analyzed animals doubly mutant for
tax-6 and a mutation that is proposed to be required for sensory signaling in AFD and ASH neurons. Our results are consistent with the model, in which TAX-6 calcineurin is activated by calcium influx through the sensory cation channel, TAX-4/TAX-2 cyclic nucleotide-gated channel or capsaicin-receptor-like OSM-9 channel, and negatively regulate the sensory signal transduction pathway. In contrast to our intuitive prediction,
tax-6 mutants however showed partially defective olfactory responses to AWA- and AWC-sensed odorants. We then explored olfactory responses further and found that partially defective olfactory responses of
tax-6 mutants are caused by hyper-activated olfactory adaptation (3). First,
tax-6 mutants were hyper-adaptable to isoamyl alcohol (iaa) sensed by AWC neurons. Second,
tax-6;
osm-9 double mutants, where
osm-9 is known to be completely defective in adaptation to iaa, showed normal responses to iaa as in wild type. Thus, it is likely that TAX-6 normally inhibits adaptation machinery in AWC neurons. Altogether, we suggest that TAX-6 calcineurin controls the efficiency of sensory neuronal activity and excitability, by negatively modulating signal transduction pathways in sensory neurons. (1) Dusenbery et al (1975), Genetics 80; 297-309. (2) Hedgecock and Russell (1975), PNAS 72; 4061-4065. (3) Colbert and Bargmann (1995), Neuron 14; 803-812.