title: Role of TARP interaction in S-SCAM-mediated regulation of AMPA receptors.
abstract: Scaffolding proteins are involved in the incorporation, anchoring, maintenance, and removal of AMPA receptors (AMPARs) at synapses, either through a direct interaction with AMPARs or via indirect association through auxiliary subunits of transmembrane AMPAR regulatory proteins (TARPs). Synaptic scaffolding molecule (S-SCAM) is a newly characterized member of the scaffolding proteins critical for the regulation and maintenance of AMPAR levels at synapses, and directly binds to TARPs through a PDZ interaction. However, the functional significance of S-SCAM-TARP interaction in the regulation of AMPARs has not been tested. Here we show that overexpression of the C-terminal peptide of TARP-γ2 fused to EGFP abolished the S-SCAM-mediated enhancement of surface GluA2 expression. Conversely, the deletion of the PDZ-5 domain of S-SCAM that binds TARPs greatly attenuated the S-SCAM-induced increase of surface GluA2 expression. In contrast, the deletion of the guanylate kinase domain of S-SCAM did not show a significant effect on the regulation of AMPARs. Together, these results suggest that S-SCAM is regulating AMPARs through TARPs.
authors.affiliation: Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Danielson
authors.forename: Jacob
authors.initials: J
authors.lastname: Metallo
authors.forename: Sang H
authors.initials: SH
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D051528:Guanylate Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D054731:PDZ Domains; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491911:Cacng2 protein, rat; C522274:Cacng4 protein, rat; D015220:Calcium Channels; C114103:Magi2 protein, rat; D018091:Receptors, AMPA; D051528:Guanylate Kinases; C104722:glutamate receptor ionotropic, AMPA 2