title: The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking.
abstract: Mutations in TSPAN7--a member of the tetraspanin protein superfamily--are implicated in some forms of X-linked intellectual disability. Here we show that TSPAN7 overexpression promotes the formation of filopodia and dendritic spines in cultured hippocampal neurons from embryonic rats, whereas TSPAN7 silencing reduces head size and stability of spines and AMPA receptor currents. Via its C terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking. These findings indicate that, in hippocampal neurons, TSPAN7 regulates AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability.
authors.affiliation: CNR Institute of Neuroscience, Department of Medical Pharmacology, University of Milan, Milan 20129, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bassani
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Cingolani
authors.forename: Pamela
authors.initials: P
authors.lastname: Valnegri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Folci
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zapata
authors.forename: Antonella
authors.initials: A
authors.lastname: Gianfelice
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Goda
authors.forename: Maria
authors.initials: M
authors.lastname: Passafaro
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011554:Pseudopodia / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D006835:Hydrazones; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; C404405:TSPAN7 protein, human; D059470:Tetraspanins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins