CAMKI and Thermosensation

Thermosensation is perhaps the most poorly understood of the sensory modalities, despite its critical role in modulating the behavior and metabolism of organisms. To investigate thermosensory neuron (AFD) function and development, we isolated mutants with defects in AFD- specific gene expression, and have identified four genes required for this process. ttx-1 encodes an OTX/OTD- like transcription factor which is both necessary and sufficient to specify AFD fate. tax-2 and tax-4 have been previously shown to encode subunits of a cGMP-gated channel that functions in thermosensory signal transduction. cmk-1 encodes the C. elegans ortholog of CAMKI, a calcium/calmodulin dependent protein kinase 1. Although CAMKI has been well characterized biochemically, the in vivo role of CAMKI is not well characterized.

cmk-1 animals have reduced AFD- specific expression of the receptor guanylate cyclase gene gcy-8, and the nuclear hormone receptor homolog nhr-38, but not ceh-14, a LIM-homeodomain protein. The cmk-1 promoter drives GFP expression in many neurons, including AFD, and CMK-1 -GFP protein is cytosolic.

cmk-1 animals have altered thermotaxis behavior, and are thermophilic, preferring temperatures warmer than the cultivation temperature. The gene expression and thermotaxis defects of cmk-1 can be rescued by a cmk-1 CDNA specifically expressed in AFD, indicating that cmk-1 function is cell autonomous for these phenotypes. Does loss of cmk-1 function have other behavioral consequences? We have preliminary evidence suggesting a role for cmk-1 in adaptation to some odorants.

cmk-1 functions in a novel pathway regulating AFD gene expression and function. Our working hypothesis is that cmk-1 does not function in thermosensory signal transduction directly, but rather is involved in adaptation to thermal cues. This adaptation may occur in the short term via CMK-1 phosphorylation of AFD signal transduction components, and in the long term by modulation of the type and quantity of signaling molecules expressed in the thermosensory neurons. For the future, we are very interested in identifying additional genes which function upstream and downstream of cmk-1.

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