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Curr Biol. 2013 Jun 3;23(11):1007-12. doi: 10.1016/j.cub.2013.04.052. Epub 2013 May 9.

Environmental alkalinity sensing mediated by the transmembrane guanylyl cyclase GCY-14 in C. elegans.

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Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.


Survival requires that living organisms continuously monitor environmental and tissue pH. Animals sense acidic pH using ion channels and G-protein-coupled receptors (GPCRs), but monitoring of alkaline pH is not well understood. We report here that in the nematode Caenorhabditis elegans, a transmembrane receptor-type guanylyl cyclase (RGC), GCY-14, of the ASEL gustatory neuron, plays an essential role in the sensing of extracellular alkalinity. Activation of GCY-14 opens a cGMP-gated cation channel encoded by tax-2 and tax-4, resulting in Ca(2+) entry into ASEL. Ectopic expression of GCY-14 in other neurons indicates that it accounts for the alkalinity sensing capability. Domain-swapping and site-directed mutagenesis of GCY-14 reveal that GCY-14 functions as a homodimer, in which histidine of the extracellular domains plays a crucial role in alkalinity detection. These results argue that in addition to ion channels and GPCRs, RGCs also play a role in pH sensation in neurons.

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