How are stabilized AMPA receptors at synapses?
Glutamate receptors of AMPA type (AMPAR) are the main players of synaptic transmission in mammalian brain. Their numbers at the synapse largely determines the efficiency of synaptic transmission and varies considerably during neuronal activity. Recent models suggest that the specific regulation of the number and organization of the synapse to AMPAR are key mechanisms involved in synaptic plasticity processes that underlie memory and learning. Understanding these processes is therefore a major challenge in neuroscience. AMPAR are part of a macromolecular complex for regulating their transport, their localization to the plasma membrane and in the synapse, as well as the regulation of their physicochemical properties.
A team from IINS (Bordeaux Neurocampus) just highlight a new protein associated with AMPA receptors. Localized in the hippocampus, Shisa6 has a crucial role for the regulation of the level of AMPAR of this structure. This work was performed in collaboration with the groups of Mansvelder H. D. and A. B. Smit in Amsterdam and is currently the subject of a thesis under joint supervision ENC between Bordeaux and Amsterdam. For this study, we used a battery of techniques available in both laboratories. By proteomic analysis we characterized AMPARs as being associated with Shisa6.
Biochemistry and immunofluorescence allowed us to locate the protein at the synaptic level. FRET experiments and mobility have shown the role of Shisa6 for maintaining receptors at the synapse and the regulation of their mobility through a set of interactions with proteins in the PSD specifically PSD95. Finally, we show that by electrophysiology Shisa6 maintains glutamatergic synaptic transmission during repeated synaptic activity.
In summary, this study demonstrates for the first time that several auxiliary proteins are involved in the stabilization of AMPA receptors at the synapse. It will therefore be important to determine what are the respective contribution of these proteins to the activity-dependent control of the stabilization of AMPA receptor, a process supposed to underlie some forms of learning and memory
Shisa6: a new auxiliary protein of AMPARs that allows their synapse stabilization and inhibits their desensitization during synaptic activity - F. Coussen, J.D. Petersen, E. Normand, D. Choquet et al. in
Contact: Dr. Françoise Coussen /Interdisciplinary Institute for Neuroscience/Bordeaux Neurocampus