title: A transmembrane accessory subunit that modulates kainate-type glutamate receptors.
abstract: Glutamate receptors play major roles in excitatory transmission in the vertebrate brain. Among ionotropic glutamate receptors (AMPA, kainate, NMDA), AMPA receptors mediate fast synaptic transmission and require TARP auxiliary subunits. NMDA receptors and kainate receptors play roles in synaptic transmission, but it remains uncertain whether these ionotropic glutamate receptors also have essential subunits. Using a proteomic screen, we have identified NETO2, a brain-specific protein of unknown function, as an interactor with kainate-type glutamate receptors. NETO2 modulates the channel properties of recombinant and native kainate receptors without affecting trafficking of the receptors and also modulates kainate-receptor-mediated mEPSCs. Furthermore, we found that kainate receptors regulate the surface expression of NETO2 and that NETO2 protein levels and surface expression are decreased in mice lacking the kainate receptor GluR6. The results show that NETO2 is a kainate receptor subunit with significant effects on glutamate signaling mechanisms in brain.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Fannie
authors.initials: F
authors.lastname: St-Gelais
authors.forename: Chad P
authors.initials: CP
authors.lastname: Grabner
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Trinidad
authors.forename: Akio
authors.initials: A
authors.lastname: Sumioka
authors.forename: Megumi
authors.initials: M
authors.lastname: Morimoto-Tomita
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Christoph
authors.initials: C
authors.lastname: Straub
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics; D051381:Rats; D018092:Kainic Acid Receptors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*; D000097806:GluK2 Kainate Receptor
chemical_list: D018698:Glutamic Acid; D008565:Membrane Proteins; D021122:Protein Subunits; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C539204:NETO2 protein, mouse