| Research Abstract |
In collaboration with Nef lab, we show that the neuron-specific calcium sensor NCS-1, a highly conserved protein through evolution, is essential for thermotaxis. ncs-1 knockout animals show strong defects in ; isothermoal tracking. The knockout phenotype can be rescued by re-introducing wild-type NCS-1 into the AIY interneuron, a key component of the thermotaxis network. A loss of function form of NCS-1 : unable to bind calcium does not restore thermotaxis, whereas overexpression of NCS-1 enhances isothermal tracking behavior. Thus, proper calcium signaling via the calcium sensor NCS-1 defines a novel pathway that is essential for associative learning and memory in C. elegans. ttx-1 mutants show cryophylic phenotype. In collaboration with Sengupta lab, we show that ttx-1 encodes a member of the highly conserved OTX/OTD homeodomain protein family, and is expressed in the AFD neurons. Misexpression of ttx-1 is sufficient to convert other sensory neurons to AFD-like fate. C. elegans animals bearing a loss-of-function mutation in TAX-6, a calcineurin A subunit, exhibit pleiotropic abnormalities including many aberrant sensory behaviors. The tax-6 mutant defect in thermosensation is consistent with hyperactivation of the AFD thermosensory neurons. Conversely, constitutive activation of TAX-6 causes a behavioral phenotype consistent with inactivation of AFD neurons. In olfactory neurons, the impaired olfactory response of tax-6 mutants to an AWC-sensed odorant is caused by hyper-adaptation, which is suppres'sible by a mutation causing defective olfactory adaptation. Taken together, our results suggest that stimulus-evoked calcium entry activates calcineurin, which in turn negatively regulates multiple aspects of sensory signaling.
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