A transmembrane accessory subunit that modulates kainate-type glutamate receptors.
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.
Zhang
Wei
W
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
St-Gelais
Fannie
F
Grabner
Chad P
CP
Trinidad
Jonathan C
JC
Sumioka
Akio
A
Morimoto-Tomita
Megumi
M
Kim
Kwang S
KS
Straub
Christoph
C
Burlingame
Alma L
AL
Howe
James R
JR
Tomita
Susumu
S
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
D018698:Glutamic Acid; D008565:Membrane Proteins; D021122:Protein Subunits; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C539204:NETO2 protein, mouse