Kainate Receptor Activation Shapes Short-Term Synaptic Plasticity by Controlling Receptor Lateral Mobility at Glutamatergic Synapses

Abstract

Kainate receptors (KARs) mediate postsynaptic currents with a key impact on neuronal excitability. However, the molecular determinants controlling KAR postsynaptic localization and stabilization are poorly understood. Here, we exploit optogenetic and single-particle tracking approaches to study the role of KAR conformational states induced by glutamate binding on KAR lateral mobility at synapses. We report that following glutamate binding, KARs are readily and reversibly trapped at glutamatergic synapses through increased interaction with the β-catenin/N-cadherin complex. We demonstrate that such activation-dependent synaptic immobilization of KARs is crucial for the modulation of short-term plasticity of glutamatergic synapses. Thus, the present study unveils the crosstalk between conformational states and lateral mobility of KARs, a mechanism regulating glutamatergic signaling, particularly in conditions of sustained synaptic activity.

Keywords: cadherin; catenin; glutamate uncaging; glutamatergic PSD; glutamatergic synapses; kainate receptors; lateral diffusion; model simulations; short-term synaptic plasticity; single-particle tracking.