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


Synaptic transmission from excitatory nerve cells in the mammalian brain is largely mediated by AMPA (α-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 head1,2,3,4. Moreover, long-term potentiation is associated with the formation of dendritic spines as well as synaptic delivery of AMPA receptors5,6,7,8. 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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Figure 1: GluR2 promotes increased number and size of spines.
Figure 2: Spine-inducing determinants of GluR2.
Figure 3: Inhibition of spine morphogenesis by Fc fusion of GluR2 NTD and siRNA knockdown of GluR2.
Figure 4: GluR2 induces dendritic spines in GABA-releasing interneurons.


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We are grateful to F. Beretta and P. Grossano for technical support. The work was supported by Telethon-Italy (M.P.), Human Frontier Science Program long-term fellowship (T.N.), the Giovanni Armenise-Harvard Foundation Career Development Program (C.S.) and NIH (M.S.). M.S. is an Investigator of the Howard Hughes Medical Institute.

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Correspondence to Maria Passafaro or Morgan Sheng.

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Passafaro, M., Nakagawa, T., Sala, C. et al. Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature 424, 677–681 (2003).

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