title: Trafficking of the NMDAR2B receptor subunit distal cytoplasmic tail from endoplasmic reticulum to the synapse.
abstract: NMDA receptor NR2A/B subunits have PDZ-binding domains on their extreme C-termini that are known to interact with the PSD-95 family and other PDZ proteins. We explore the interactions between PSD-95 family proteins and the NR2A/B cytoplasmic tails, and the consequences of these interactions, from the endoplasmic reticulum (ER) through delivery to the synapse in primary rat hippocampal and cortical cultured neurons. We find that the NR2A/B cytoplasmic tails cluster very early in the secretory pathway and interact serially with SAP102 beginning at the intermediate compartment, and then PSD-95. We further establish that colocalization of the distal C-terminus of NR2B and PSD-95 begins at the trans-Golgi Network (TGN). Formation of NR2B/PSD-95/SAP102 complexes is dependent on the PDZ binding domain of NR2B subunits, but association with SAP102 and PSD-95 plays no distinguishable role in cluster pre-formation or initial targeting to the vicinity of the synapse. Instead the PDZ binding domain plays a role in restricting cell-surface clusters to postsynaptic targets.
authors: Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, California, United States of America. sstandley@westernu.edu
authors: Steve
authors: S
authors: Standley
authors: Ronald S
authors: RS
authors: Petralia
authors: Manneth
authors: M
authors: Gravell
authors: Rebecca
authors: R
authors: Hamilton
authors: Ya-Xian
authors: YX
authors: Wang
authors: Manfred
authors: M
authors: Schubert
authors: Robert J
authors: RJ
authors: Wenthold
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate