title: Presynaptic PICK1 facilitates trafficking of AMPA-receptors between active zone and synaptic vesicle pool.
abstract: Previous studies have indicated that presynaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) contribute to the regulation of neurotransmitter release. In hippocampal synapses, the presynaptic surface expression of several AMPAR subunits, including GluA2, is regulated in a ligand-dependent manner. However, the molecular mechanisms underlying the presynaptic trafficking of AMPARs are still unknown. Here, using bright-field immunocytochemistry, western blots, and quantitative immunogold electron microscopy of the hippocampal CA1 area from intact adult rat brain, we demonstrate the association of AMPA receptors with the presynaptic active zone and with small presynaptic vesicles, in Schaffer collateral synapses in CA1 of the hippocampus. Furthermore, we show that GluA2 and protein interacting with C kinase 1 (PICK1) are colocalized at presynaptic vesicles. Similar to postsynaptic mechanisms, overexpression of either PICK1 or pep2m, which inhibit the N-ethylmaleimide sensitive fusion protein (NSF)-GluA2 interaction, decreases the concentration of GluA2 in the presynaptic active zone membrane. These data suggest that the interacting proteins PICK1 and NSF act as regulators of presynaptic GluA2-containing AMPAR trafficking between the active zone and a vesicle pool that may provide the basis of presynaptic components of synaptic plasticity.
authors.affiliation: Institute of Basic Medical Sciences, Division of Anatomy, University of Oslo, Oslo, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Haglerød
authors.affiliation: Institute of Basic Medical Sciences, Division of Anatomy, University of Oslo, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Hussain
authors.affiliation: School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: J
authors.initials: J
authors.lastname: Xia
authors.affiliation: Institute of Basic Medical Sciences, Division of Anatomy, University of Oslo, Oslo, Norway.
authors.forename: F-M S
authors.initials: FS
authors.lastname: Haug
authors.affiliation: Institute of Basic Medical Sciences, Division of Anatomy, University of Oslo, Oslo, Norway.
authors.forename: O P
authors.initials: OP
authors.lastname: Ottersen
authors.affiliation: School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Henley
authors.affiliation: Institute of Basic Medical Sciences, Division of Anatomy, University of Oslo, Oslo, Norway. Electronic address: svend.davanger@medisin.uio.no.
authors.forename: S
authors.initials: S
authors.lastname: Davanger
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D046509:Tissue Culture Techniques
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D018091:Receptors, AMPA; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPA; PICK1; electron microscopy; hippocampus; receptor trafficking; synaptic plasticity