The NMDAR subunit NR3A is most highly expressed during the second postnatal week, when synaptogenesis reaches peak levels. Genetic ablation or overexpression of the NR3A subunit negatively interferes with the maturation of cortical synapses and leads to changes in the shape and number of dendritic spines, the density of which is increased in NR3A knock-out mice and decreased in NR3A-overexpressing transgenic mice. Alterations in spine density have been linked to dysregulation of mTOR signaling and synaptic protein translation. Using a yeast two-hybrid system, we identified the mTOR-activating GTPase Rheb as an interacting protein of the NMDAR subunit NR3A. We confirmed the interaction in mammalian cells by expressing recombinant Rheb and NR3A and showed that Rheb and NR3A could be co-immunoprecipitated from synaptic plasma membranes from the developing rat brain. These data suggest that NR3A sequesters synaptic Rheb and might thus function as a break of the mTOR-dependent synaptic translation of protein.
© 2010 S. Karger AG, Basel
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Prof. Nikolaus J. Sucher
The Centre for Complementary Medicine Research
University of Western Sydney, Locked Bag 1797
Penrith, NSW 2751 (Australia)
Tel. +61 2 4620 3345, Fax +61 2 4620 3017, E-Mail email@example.com
Received: July 27, 2010
Accepted after revision: October 20, 2010
Published online: December 7, 2010
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 0, Number of References : 27
Vol. 18, No. 4, Year 2010 (Cover Date: March 2011)
Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)
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