title: Single amino acid residue in the M4 domain of GluN1 subunit regulates the surface delivery of NMDA receptors.
abstract: N-methyl-D-aspartate (NMDA) receptors are glutamate ion channels that are critically involved in excitatory synaptic transmission and plasticity. The functional NMDA receptor is a heterotetramer composed mainly of GluN1 and GluN2 subunits. It is generally thought that only correctly assembled NMDA receptors can pass the quality control checkpoint in the endoplasmic reticulum (ER) and are transported to the cell surface membranes. The molecular mechanisms underlying these processes remain poorly understood. Using chimeric and mutated GluN1 subunits expressed in heterologous cells, we identified a single amino acid residue within the fourth membrane domain (M4) of GluN1 subunit, L830, that regulates the surface number of NMDA receptors. Our experiments show that this residue is not critical for the interaction between GluN1 and GluN2 subunits or for the formation of functional receptors, but rather that it regulates the forward trafficking of the NMDA receptors. The surface expression of both GluN2A- and GluN2B-containing receptors is regulated by the L830 residue in a similar manner. We also found that the L830 residue is not involved in the trafficking of individually expressed GluN1 subunits. Our data reveal a critical role of the single amino acid residue within the GluN1 M4 domain in the surface delivery of functional NMDA receptors.
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.forename: Katarina
authors.initials: K
authors.lastname: Lichnerova
authors.forename: Ladislav
authors.initials: L
authors.lastname: Vyklicky
authors.forename: Martin
authors.initials: M
authors.lastname: Horak
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016296:Mutagenesis / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate