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Dissecting glycine neurotransmission: facts and questions| old_uid | 3269 |
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| title | Dissecting glycine neurotransmission: facts and questions |
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| start_date | 2007/10/15 |
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| schedule | 14h30 |
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| online | no |
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| location_info | amphi PA Louis |
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| details | Invité par Pierre Mothet, Inserm U 862 |
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| summary | Besides GABA, glycine is the major inhibitory neurotransmitter in the mammalian CNS. In addition, it is thought to serve as a coagonist of NMDA receptors. Upon Ca2+ triggered release from glycinergic nerve terminals, glycine causes post synaptic inhibition by binding to strychnine-sensotive glycine receptors (GlyRs) that are densely clustered in the postsynaptic membrane. The synaptic localization of GlyRs requires the scaffolding protein gephyrin which also is found at GABAergic synapses. Glycinergic neurotransmission is terminated by the reuptake of glycine into glycinergic nerve terminals and neighboring glial cells via Na+/Cl--dependent glycine transporters, GlyT1 and GlyT2. We have used transfection of primary neurons and gene targeting to dissect the physiological functions of distinct GlyR subtypes and GlyT isoforms and to address the mechanisms underlying the synaptic clustering of these membrane proteins. Accordingly, distinct GlyR subtypes have different roles in the regulation of motor and sensory functions, whereas GlyT1 and GlyT2 are required for transmitter removal and recycling, respectively. Inactivation of the gephyrin gene causes lethality, due to impaired postsynaptic GlyR and GABAA receptor clustering. Similarly, knock-out of the gephyrin-binding GEF collybistin leads to a region-specific loss of post-synaptic GABAA receptors. Together, our results disclose vital roles of specific glycine receptors and glycine transporters and highlight the importance of specific scaffolding proteins in inhibitory synapse formation. |
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| oncancel | horaire et lieu inhabituels |
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| responsibles | Deris |
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