| 日 時 | 2018年05月21日(月) 16:30 |
|---|---|
| 講演者 | Dr. Marc Gielen |
| 講演者所属 | Permanent researcher, Channel Receptors Unit, CNRS- Institut Pasteur (Paris, France) |
| 場 所 | 生理学研究所（明大寺地区）1階 セミナー室 |
| お問い合わせ先 |
久保義弘(神経機能素子研究部門) ykubo(a)nips.ac.jp） |
| 要旨 |
Eukaryotic pentameric ligand-gated ion channels (pLGICs), such as the inhibitory GABAA receptors (GABAARs) and the nicotinic acetylcholine receptors (nAChRs), are neurotransmitter-gated ion channels mediating fast synaptic transmission in the nervous system. Classical pLGICs are heteromers of varying stoichiometries, often incorporating several copies of the neurotransmitter-binding subunits and additional accessory subunits. Recombinant expression of the receptors’ subunits thus usually results in a mixture of heterogeneous receptor populations at the plasma membrane, complicating the analysis of their functional properties. To overcome this difficulty, I have built a series of concatemeric pLGICs, whereby all subunits are linked covalently together. This allows for the precise control of subunits’ stochiometry. It also enables to introduce mutations in each subunit one by one, in order to examine the contribution of each individual subunit to the receptors’ gating and pharmacology. I will illustrate the benefits of such strategy with two projects: 1) understanding the crosstalk between subunits during the desensitization of α1ß2γ2 GABAARs; and 2) unraveling the pharmacological properties of α5-containing nAChRs, which are key players in nicotine addiction.
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