CJM2-2019: Ligand-gated ion channels from atomic structure to synaptic transmission
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Communication between neurons is primarily performed by chemical synapses, which promote either excitatory or inhibitory transmission. The time course and strength of synaptic communication is regulated by a wide range of chemical signals, underlying the unique ability of neuronal networks to compute and store information. Central to the complex machinery of chemical synapses are ligand-gated ion channels (LGICs), that sense the neurotransmitters released from the presynaptic compartment, converting this chemical signal into an electrical signal through the opening of their intrinsic ion channel. LGICs are thus highly dynamic allosteric proteins, and their study has been revolutionized by recent advances in biochemistry and X-ray crystallography techniques as well as, more recently, by single particle cryo-electron microscopy. Together with electrophysiology and fluorescence techniques at the ensemble and single molecule level, as well as molecular dynamic simulation and mass spectrometry, the molecular mechanisms of signal transduction, and their regulation by drugs, lipids and associated proteins is being emerging. This meeting will show the current advances on the major classes of receptors, notably the trimeric P2X (ATP-gated purinergic receptors) and ASICs (acid-sensing ion channels), the tetrameric glutamate receptors, as well as the pentameric receptors, including nicotinic acetylcholine, 5-HT3 serotonin, glycine and γ-aminobutyric GABAA receptors. Other channels and receptors including GPCRs will also be presented. In addition, pLGICs will also be replaced in the synaptic context, and their interaction with accessory and scaffolding proteins, as well as their mobility, diffusion and aggregation will be addressed using cutting edge imaging techniques. Throughout the sessions, we will also address how the fundamental knowledge gathered by combined structural and functional approaches is currently applied to invent novel chemical tools such as light-activated channels, as well as to develop new classes of allosteric effectors.