Ichiro N Maruyama
Okinawa Institute of Science and Technology, Japan
Scientific Tracks Abstracts: Neurochem Neuropharm
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 cGMPgated cation channel encoded by tax-2 and tax-4 genes, resulting in Ca2+ 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. The Ca2+ entry into the cilia of ASEL induces depolarization of the cilial membrane potential, which in turn activates L-type voltage-gated Ca2+ channels containing an EGL-19 a subunit for active propagation of electrical signals in the dendrite. These results argue that in addition to ion channels and GPCRs, RGCs also play a role in pH sensation in neurons.
Ichiro N Maruyama is a Professor at the Okinawa Institute of Science and Technology Graduate University (OIST). He received his PhD from The University of Tokyo, Japan. Subsequently, he was trained as a Post-doctoral fellow in MRC Laboratory of Molecular Biology, Cambridge, UK, where he started to work on the nematode Caenorhabditis elegans with an interest in its nervous system. He then moved to The Scripps Research Institute, La Jolla, California, USA, where he started to study molecular mechanisms underlying activation of cell-surface receptors. At OIST, he continues to work on learning, memory and decision-making in C. elegans as well as on molecular mechanisms of transmembrane signaling mediated by cell-surface receptors.