Neto2 modulation of kainate receptors with different subunit compositions

Kainate receptors are less well understood than other glutamate receptors, and synaptic kainate receptors display properties that differ from recombinant receptors. In particular, the slow decay of kainate receptor synaptic currents contrasts with the rapid deactivation and desensitization of receptors expressed in heterologous cells. We recently identified Neuropilin and Tolloid like-2 (Neto2) as a novel accessory subunit of kainate receptors and showed that Neto2 modulates the gating kinetics of GluK2 receptors. However, the kainate receptor family consists of five different subunits (GluK1-5) that can form homomeric and heteromeric receptors with different functional properties. Here, we tested whether Neto2 modulation varies with subunit composition. Rapid application techniques were used to apply glutamate to outside-out patches that contained GluK1, GluK1/5, or GluK2/5 kainate receptors. Coexpression of Neto2 slowed desensitization to varying degrees. Responses to 1 ms pulses of glutamate were also slowed by Neto2, especially for receptors containing GluK5, as were postsynaptic currents in neurons expressing recombinant kainate receptors. In addition, Neto2 markedly increased the rate at which some receptors recovered from desensitization. These results suggest that Neto2 modulates the function of most kainate receptors.