title: Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors.
abstract: N-methyl-D-aspartate (NMDA) receptors mediate fast excitatory synaptic transmission in the mammalian central nervous system. The activation of NMDA receptors plays a key role in brain development, synaptic plasticity, and memory formation, and is a major contributor to many neuropsychiatric disorders. Here, we investigated the mechanisms that underlie the trafficking of GluN1/GluN2C receptors. Using an approach combining molecular biology, microscopy, and electrophysiology in mammalian cell lines and cultured cerebellar granule cells, we found that the surface delivery of GluN2C-containing receptors is reduced compared to GluN2A- and GluN2B-containing receptors. Furthermore, we identified three distinct regions within the N-terminus, M3 transmembrane domain, and C-terminus of GluN2C subunits that are required for proper intracellular processing and surface delivery of NMDA receptors. These results shed new light on the regulation of NMDA receptor trafficking, and these findings can be exploited to develop new strategies for treating some forms of neuropsychiatric disorders.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Prague Czech Republic ; Department of Physiology, Faculty of Science, Charles University in Prague Prague, Czech Republic.
authors.forename: Katarina
authors.initials: K
authors.lastname: Lichnerova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Prague Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Kaniakova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Prague Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Skrenkova
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Prague Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Vyklicky
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i., Prague Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Horak
keywords: cerebellar granule cells; electrophysiology; endoplasmic reticulum; glutamate receptor; intracellular trafficking; ion channel