| Abstract No.: | 303 |
| Country: | Canada |
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| Title: | NEW INSIGHTS INTO THE STRUCTURE AND FUNCTION OF FAST-GATED IONOTROPIC GLUTAMATE RECEPTORS |
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| Authors/Affiliations: | 1 Adrian Wong*;
1 Ottawa Health Research Institute, ON, Canada
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| Content: | Ionotropic glutamate receptors (iGluRs) are one of the most widespread signaling proteins in the mammalian brain. Two closely-related family members, namely the AMPA- and Kainate-selective iGluRs, have considerable overlap in terms of structure and function and therefore it has been assumed that their gating mechanisms are identical too. However, the kinetic properties of synaptic AMPARs and KARs are different suggesting that functional differences may exist between them. In support of this, we have recently identified a molecular mechanism that distinguishes between the functional properties of both receptor subtypes. Specifically, we have identified a novel ion-binding domain for external Na+ and Cl- ions that must be occupied if KARs are to respond to their neurotransmitter, L-glutamate. This is achieved by the formation of a dipole that operates by coupling neurotransmitter binding to KAR channel activation. Interestingly, this mechanism is absent from both AMPARs and NMDARs, suggesting that this novel gating feature evolved sometime after distinct iGluR families had already been established. The sensitivity of KARs to external ions enables them to act as “ion-sensors” that may regulate receptor trafficking and/or neuronal activity in the central nervous system. |
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