title: Amino-terminal domains of kainate receptors determine the differential dependence on Neto auxiliary subunits for trafficking.
abstract: The kainate receptor (KAR), a subtype of glutamate receptor, mediates excitatory synaptic responses at a subset of glutamatergic synapses. However, the molecular mechanisms underlying the trafficking of its different subunits are poorly understood. Here we use the CA1 hippocampal pyramidal cell, which lacks KAR-mediated synaptic currents, as a null background to determine the minimal requirements for the extrasynaptic and synaptic expression of the GluK2 subunit. We find that the GluK2 receptor itself, in contrast to GluK1, traffics to the neuronal surface and synapse efficiently and the auxiliary subunits Neto1 and Neto2 caused no further enhancement of these two trafficking processes. However, the regulation of GluK2 biophysical properties by Neto proteins is the same as that of GluK1. We further determine that it is the amino-terminal domains (ATDs) of GluK1 and GluK2 that control the strikingly different trafficking properties between these two receptors. Moreover, the ATDs are critical for synaptic expression of heteromeric receptors at mossy fiber-CA3 synapses and also mediate the differential dependence on Neto proteins for surface and synaptic trafficking of GluK1 and GluK2. These results highlight the fundamental differences between the two major KAR subunits and their interplay with Neto auxiliary proteins.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143.
authors.forename: Nengyin
authors.initials: N
authors.lastname: Sheng
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143.|Model Animal Research Center, Key Laboratory of Model Animal for Disease Study of Ministry of Education, Nanjing University, Nanjing 210061, People's Republic of China.
authors.forename: Yun Stone
authors.initials: YS
authors.lastname: Shi
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143; roger.nicoll@ucsf.edu.|Department of Physiology, University of California, San Francisco, CA 94143.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D019281:Dimerization; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D055369:Miniature Postsynaptic Potentials / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D000072417:Protein Domains; D060066:Protein Interaction Maps; D021381:Protein Transport / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000502:physiology; D000097806:GluK2 Kainate Receptor
chemical_list: D026502:LDL-Receptor Related Proteins; D008565:Membrane Proteins; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000097806:GluK2 Kainate Receptor; C486748:Neto1 protein, mouse; C000610545:Neto2 protein, rat
keywords: Neto proteins; amino-terminal domain; kainate receptor; synaptic trafficking