Editors' ChoiceNeuroscience

New Role for Glutamate Receptor Subunit

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Science's STKE  12 Aug 2003:
Vol. 2003, Issue 195, pp. tw311-TW311
DOI: 10.1126/stke.2003.195.tw311

Excitatory synapses on hippocampal neurons in the mammalian brain are located on top of dendritic spines. Increased formation of spines, protuberances on the postsynaptic cell, is thought to be part of the mechanism by which long-term changes are stored in neurons and maintained after stimulation. AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors often mediate excitatory signals, and Passafaro et al. explored the role of the glutamate receptor 2 (GluR2) subunit of AMPA receptors on spine formation in cultured hippocampal neurons from embryonic rats. Overexpression of GluR2 increased the number of spines and their size, whereas treatment of cells with small interfering RNA to decrease expression of endogenous GluR2 decreased the size and number of spines. Surprisingly, these effects appeared to require only the extracellular N-terminal domain of the receptor and thus may be independent of the better-understood channel properties of the receptor or its C-terminal portion, which interacts with a number of cytoplasmic proteins. The authors discuss mechanisms by which the GluR2 subunits might act. A favored model is that GluR2 mediates interaction with another protein, which might be present in either soluble form or anchored in the membrane of pre- or postsynaptic cells. Such an interacting protein itself, or another interaction partner, might mediate signaling that promotes growth of spines.

M. Passafaro, T. Nakagawa, C. Sala, M. Sheng, Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature 424, 677-681 (2003). [Online Journal]

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