Synaptic Targeting of Kainate Receptors

When native and recombinant kainate receptors (KARs) are compared, there is a mismatch in several of their functional properties. While both generate currents, synaptic responses mediated by KARs have rarely observed in cultured hippocampal neurons. The recent discovery of auxiliary proteins for KARs, such as Netos, offers an explanation for these discrepancies. We found that the GluK5 KAR subunit and the ancillary proteins, Neto1 and Neto2, are not expressed by hippocampal neurons in culture. Therefore, we used this model to directly test whether these proteins are required for the synaptic localization of KARs. Transfection of GluK4, GluK5, Neto1, or Neto2 into hippocampal neurons was associated with the appearance of synaptic KAR-mediated EPSCs. However, GluK4 or GluK5 alone produced synaptic activity in a significant proportion of cells and with reliable event frequency. While neurons expressing GluK4 or GluK5 subunits displayed synaptic responses with rapid kinetics, the expression of Neto proteins conferred these synaptic responses with their characteristic slow onset and decay rates. These data reveal some requirements for KAR targeting to the synapse, indicating a fundamental role of high affinity KAR subunits in this process.