| 研究実績の概要 |
Prrt3 is an orphan metabotropic receptor of family C GPCRs. There is no publication concerning Prrt3 and the physiological roles and functioning mechanisms of Prrt3 are totally unknown. We previously observed that Prrt3 is highly expressed in mouse brain and the homozygous Prrt3 KO mice show high mortality. Therefore, Prrt3 may play important roles in the brain function.
In the present research project, we aim to clarify the physiological ligand and activation mechanisms of Prrt3. We have perform molecular biological, electrophysiological and [Ca2+]i imaging experiments using Xenopus oocytes and HEK293 cells, and we observed the following results: (1) by monitoring Gi/o protein-gated inwardly rectifying K+ (GIRK) currents and Gq-mediated Ca2+-activated Cl- current in Prrt3-expressing cells, we observed that Gi/o, but not Gq, is coupled with Prrt3; (2) by monitoring GIRK currents, we screened several types of neurotransmitter libraries and observed that some muscarinic receptor agonists, but not ACh, slightly activates the Prrt3. We also happened to identify a novel activator of GIRK channel, ivermectin, and several GIRK inhibitors. We have clarified the activation mechanisms of GIRK channel by ivermectin and published the data and results in The Journal of Physiology; (3) Prrt3 is not activated by the cleavage of its N-terminal extracellular domain.
This research project provide us with information toward the identification of the ligand of Prrt3 and its activation mechanisms. This advance our understanding about the synaptic transmission by a novel mechanism.
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