title: Ligand binding of PDZ domains has various roles in the synaptic clustering of SAP102 and PSD-95.
abstract: Synapse-associated protein 102 (SAP102) and postsynaptic density-95 (PSD-95) bind to NMDA receptors through PDZ domains and cluster at excitatory postsynaptic sites called postsynaptic densities (PSD). We previously reported that PSD-95 containing mutated PDZ domains incapable of ligand binding clustered at synaptic sites with reduced efficiency. Here, we compared the synaptic clustering of the same series of full-length SAP102 mutants in hippocampal neurons. Unexpectedly, ligand-binding deficient mutant SAP102 showed more efficient synaptic localization than wild-type SAP102. Further, when SAP102-PDZ mutants were co-expressed with either the GluN2A or GluN2B NMDA receptor subunit, both subunits showed decreased synaptic clustering, although the mutants were efficiently targeted to the synapses. This finding suggests that direct binding of NMDA receptors with SAP102 is involved in the efficient targeting of NMDA receptors to the synapses, whereas ligand binding of the PDZ domains is not essential for the synaptic clustering of SAP102.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Minatohara
authors.forename: Sho-hei
authors.initials: SH
authors.lastname: Ichikawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Seki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Doi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D054731:PDZ Domains; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008024:Ligands; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C501447:Dlg4 protein, mouse; C121001:NR2B NMDA receptor; C491075:Dlgh3 protein, mouse