Association of the small GTPase Rheb with the NMDA receptor subunit NR3A.
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.
Centre for Complementary Medicine Research, University of Western Sydney, Penrith South DC, NSW, Australia. n.sucher@uws.edu.au
Nikolaus J
NJ
Sucher
Eric
E
Yu
Shing Fai
SF
Chan
Mitra
M
Miri
Benjamin J
BJ
Lee
Bo
B
Xiao
Paul F
PF
Worley
Frances E
FE
Jensen
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013570:Synaptic Membranes / Q000201:enzymology / Q000235:genetics
C464437:NR3A NMDA receptor; D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D016194:Receptors, N-Methyl-D-Aspartate; D020559:Monomeric GTP-Binding Proteins