title: Modulation of GluK2a subunit-containing kainate receptors by 14-3-3 proteins.
abstract: Kainate receptors (KARs) are one of the ionotropic glutamate receptors that mediate excitatory postsynaptic currents (EPSCs) with characteristically slow kinetics. Although mechanisms for the slow kinetics of KAR-EPSCs are not totally understood, recent evidence has implicated a regulatory role of KAR-associated proteins. Here, we report that decay kinetics of GluK2a-containing receptors is modulated by closely associated 14-3-3 proteins. 14-3-3 binding requires PKC-dependent phosphorylation of serine residues localized in the carboxyl tail of the GluK2a subunit. In transfected cells, 14-3-3 binding to GluK2a slows desensitization kinetics of both homomeric GluK2a and heteromeric GluK2a/GluK5 receptors. Moreover, KAR-EPSCs at mossy fiber-CA3 synapses decay significantly faster in the 14-3-3 functional knock-out mice. Collectively, these results demonstrate that 14-3-3 proteins are an important regulator of GluK2a-containing KARs and may contribute to the slow decay kinetics of native KAR-EPSCs.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Sun
authors.forename: Haifa
authors.initials: H
authors.lastname: Qiao
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuying
authors.initials: Y
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D051381:Rats; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism*; D000097806:GluK2 Kainate Receptor
chemical_list: D048948:14-3-3 Proteins; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor
keywords: 14-3-3 Proteins; Channel Kinetics; Glutamate Receptors; Kainate Receptors; Phosphorylation; Protein Kinase C (PKC); Protein/Protein Interactions; Receptor Desensitization