Kainate receptor trafficking

Abstract

Kainate receptors (KARs) are ligand-gated ion channels that can regulate neuronal network activity and are involved in processes ranging from neuronal development and differentiation to neurodegeneration and neuronal cell death. They are tetrameric assemblies which can comprise different subunit combinations and are differentially targeted to specific cell surface compartments including preand postsynaptic membranes where they perform distinct functional roles. The processes regulating the constitutive and activity-dependent trafficking of KARs are subtle and complex. Intricate combinations of protein-protein interactions and post-translational modifications orchestrate their surface membrane delivery, residence time, internalization, and recycling or degradation. Furthermore, in addition to regulating surface expression, interacting proteins connect receptors to anchoring and signaling pathways. Although our knowledge of the processes that regulate KAR trafficking is far from complete, there has been significant progress toward defining the roles of many of these protein partners and post-translational modifications. 

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

“…Although there is a strong base of knowledge about the activity-dependent regulation of KAR endocytosis and recycling [13,15,[67][68][69][70][71], compared to AMPARs [72] and tsVSVG cargo [73], little is known about the activitydependence of secretory pathway trafficking of KARs. A very recent study reported that secretory pathway KAR trafficking is indeed highly regulated in multiple different cellular activity contexts [48].…”

Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

“…Kainate receptors (KARs) are tetrameric assemblies of combinations of GluK1 -GluK5 subunits. They are present at both pre-and postsynaptic membranes where they perform distinct roles in modulating synaptic transmission, neuronal excitability and network activity 5,6 , and are implicated in processes ranging from neuronal development and differentiation to neurodegeneration and neuronal cell death 5,7 . In addition to direct ionotropic signalling, KARs also signal through the activation of G proteins leading to PKC activation 5,6,[8][9][10] .…”

Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

“…We used the KAR subunit GluK2 as a prototypic iGluR cargo. KARs are present at both pre- and postsynaptic membranes, where they perform distinct roles in modulating synaptic transmission, neuronal excitability, and network activity ( Contractor et al., 2011 , Lerma and Marques, 2013 ), and they are implicated in processes ranging from neuronal development and differentiation to neurodegeneration and neuronal cell death ( Contractor et al., 2011 , González-González et al., 2012 ).…”