Extracellular interactions between GluR2 and N-cadherin in spine regulation.
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.
Saglietti
Laura
L
DTI Dulbecco Telethon Institute, CNR Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, Italy.
Dequidt
Caroline
C
Kamieniarz
Kinga
K
Rousset
Marie-Claude
MC
Valnegri
Pamela
P
Thoumine
Olivier
O
Beretta
Francesca
F
Fagni
Laurent
L
Choquet
Daniel
D
Sala
Carlo
C
Sheng
Morgan
M
Passafaro
Maria
M
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
D015820:Cadherins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; C104722:glutamate receptor ionotropic, AMPA 2