title: Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2.
abstract: alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors undergo constitutive and ligand-induced internalization that requires dynamin and the clathrin adaptor complex AP-2. We report here that an atypical basic motif within the cytoplasmic tails of AMPA-type glutamate receptors directly associates with mu2-adaptin by a mechanism similar to the recognition of the presynaptic vesicle protein synaptotagmin 1 by AP-2. A synaptotagmin 1-derived AP-2 binding peptide competes the interaction of the AMPA receptor subunit GluR2 with AP-2mu and increases the number of surface active glutamate receptors in living neurons. Moreover, fusion of the GluR2-derived tail peptide with a synaptotagmin 1 truncation mutant restores clathrin/AP-2-dependent internalization of the chimeric reporter protein. These data suggest that common mechanisms regulate AP-2-dependent internalization of pre- and postsynaptic membrane proteins.
authors.affiliation: Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kastning
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kukhtina
authors.forename: Josef T
authors.initials: JT
authors.lastname: Kittler
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.forename: Arndt
authors.initials: A
authors.lastname: Pechstein
authors.forename: Sven
authors.initials: S
authors.lastname: Enders
authors.forename: Sang Hyoung
authors.initials: SH
authors.lastname: Lee
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
mesh_terms: D033983:Adaptor Protein Complex mu Subunits / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D024361:Amino Acids, Basic / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D018091:Receptors, AMPA / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism
chemical_list: D033983:Adaptor Protein Complex mu Subunits; D024361:Amino Acids, Basic; D002966:Clathrin; D010455:Peptides; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; D050863:Synaptotagmin I; C104722:glutamate receptor ionotropic, AMPA 2