Molecular determinants of kainate receptor trafficking

Glutamate receptors of the kainate subtype are ionotropic receptors that play a key role in the modulation of neuronal network activity. The role of kainate receptors depends on their precise membrane and subcellular localization in presynaptic, extrasynaptic and postsynaptic domains. These receptors are composed of the combination of five subunits, three of them having several splice variants. The subunits and splice variants show great divergence in their C-terminal cytoplasmic tail domains, which have been implicated in intracellular trafficking of homomeric and heteromeric receptors. Differential trafficking of kainate receptors to specific neuronal compartments likely relies on interactions between the different kainate receptor subunits with distinct subsets of protein partners that interact with C-terminal domains. These C-terminal domains have also been implicated in the degradation of kainate receptors. Finally, the phosphorylation of the C-terminal domain regulates receptor trafficking and function. This review summarizes our knowledge on the regulation of membrane delivery and trafficking of kainate receptors implicating C-terminal domains of the different isoforms and focuses on the identification and characterization of the function of interacting partners.