title: Extracellular interactions between GluR2 and N-cadherin in spine regulation.
abstract: Via its extracellular N-terminal domain (NTD), the AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons. Here we show that the first N-terminal 92 amino acids of the extracellular domain are necessary and sufficient for GluR2's spine-promoting activity. Moreover, overexpression of this extracellular domain increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Biochemically, the NTD of GluR2 can interact directly with the cell adhesion molecule N-cadherin, in cis or in trans. N-cadherin-coated beads recruit GluR2 on the surface of hippocampal neurons, and N-cadherin immobilization decreases GluR2 lateral diffusion on the neuronal surface. RNAi knockdown of N-cadherin prevents the enhancing effect of GluR2 on spine morphogenesis and mEPSC frequency. Our data indicate that in hippocampal neurons N-cadherin and GluR2 form a synaptic complex that stimulates presynaptic development and function as well as promoting dendritic spine formation.
authors.affiliation: DTI Dulbecco Telethon Institute, CNR Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Saglietti
authors.forename: Caroline
authors.initials: C
authors.lastname: Dequidt
authors.forename: Kinga
authors.initials: K
authors.lastname: Kamieniarz
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Rousset
authors.forename: Pamela
authors.initials: P
authors.lastname: Valnegri
authors.forename: Olivier
authors.initials: O
authors.lastname: Thoumine
authors.forename: Francesca
authors.initials: F
authors.lastname: Beretta
authors.forename: Laurent
authors.initials: L
authors.lastname: Fagni
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.forename: Morgan
authors.initials: M
authors.lastname: Sheng
authors.forename: Maria
authors.initials: M
authors.lastname: Passafaro
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013131:Spine / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; C104722:glutamate receptor ionotropic, AMPA 2