title: SAP90 binds and clusters kainate receptors causing incomplete desensitization.
abstract: The mechanism of kainate receptor targeting and clustering is still unresolved. Here, we demonstrate that members of the SAP90/PSD-95 family colocalize and associate with kainate receptors. SAP90 and SAP102 coimmunoprecipitate with both KA2 and GluR6, but only SAP97 coimmunoprecipitates with GluR6. Similar to NMDA receptors, GluR6 clustering is mediated by the interaction of its C-terminal amino acid sequence, ETMA, with the PDZ1 domain of SAP90. In contrast, the KA2 C-terminal region binds to, and is clustered by, the SH3 and GK domains of SAP90. Finally, we show that SAP90 coexpressed with GluR6 or GluR6/KA2 receptors alters receptor function by reducing desensitization. These studies suggest that the organization and electrophysiological properties of synaptic kainate receptors are modified by association with members of the SAP90/PSD-95 family.
authors.affiliation: Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Garcia
authors.forename: S
authors.initials: S
authors.lastname: Mehta
authors.forename: L A
authors.initials: LA
authors.lastname: Blair
authors.forename: D G
authors.initials: DG
authors.lastname: Wells
authors.forename: J
authors.initials: J
authors.lastname: Shang
authors.forename: T
authors.initials: T
authors.lastname: Fukushima
authors.forename: J R
authors.initials: JR
authors.lastname: Fallon
authors.forename: C C
authors.initials: CC
authors.lastname: Garner
authors.forename: J
authors.initials: J
authors.lastname: Marshall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011940:Receptor Aggregation / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D000074407:SAP90-PSD95 Associated Proteins; D014018:Tissue Distribution; D000097806:GluK2 Kainate Receptor
chemical_list: D009419:Nerve Tissue Proteins; D018092:Kainic Acid Receptors; D000074407:SAP90-PSD95 Associated Proteins; D000097806:GluK2 Kainate Receptor