Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2.

Full Abstract

Synaptic transmission from excitatory nerve cells in the mammalian brain is largely mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors located at the surface of dendritic spines. The abundance of postsynaptic AMPA receptors correlates with the size of the synapse and the dimensions of the dendritic spine head. Moreover, long-term potentiation is associated with the formation of dendritic spines as well as synaptic delivery of AMPA receptors. The molecular mechanisms that coordinate AMPA receptor delivery and spine morphogenesis are unknown. Here we show that overexpression of the glutamate receptor 2 (GluR2) subunit of AMPA receptors increases spine size and density in hippocampal neurons, and more remarkably, induces spine formation in GABA-releasing interneurons that normally lack spines. The extracellular N-terminal domain (NTD) of GluR2 is responsible for this effect, and heterologous fusion proteins of the NTD of GluR2 inhibit spine morphogenesis. We propose that the NTD of GluR2 functions at the cell surface as part of a receptor-ligand interaction that is important for spine growth and/or stability.

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Author information

Author/s: Passafaro, Maria (M); Nakagawa, Terunaga (T); Sala, Carlo (C); Sheng, Morgan (M);

Affiliation: DTI Dulbecco Telethon Institute, Cellular and Molecular Pharmacology, Department of Pharmacology, University of Milan, 20129 Italy. m.passafaro(-atsign-)in.cnr.it

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Nature (Nature), published in England. (Language: eng)

Reference: 2003-Aug; vol 424 (issue 6949) : pp 677-81

Dates: Created 2003/08/07; Completed 2003/08/25; Revised 2006/11/15;

PMID: 12904794, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Nature. 2003 Aug 7;424(6949):627-8. (PMID: 12904774)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
COS Cells
Cell Size
Cells, Cultured
Dendrites - physiology
Hippocampus - cytology; metabolism
Humans

Interneurons - cytology; metabolism
Protein Structure, Tertiary
RNA, Small Interfering - genetics; metabolism
Rats
Receptors, AMPA - chemistry; genetics; metabolism
Recombinant Fusion Proteins - chemistry; genetics; metabolism
gamma-Aminobutyric Acid - metabolism

Associated Chemicals: RNA, Small Interfering (0) ; Receptors, AMPA (0) ; Recombinant Fusion Proteins (0) ; glutamate receptor ionotropic, AMPA 1 (0) ; glutamate receptor ionotropic, AMPA 2 (0) ; gamma-Aminobutyric Acid (56-12-2)

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