Trafficking of NMDA Receptors

Wenthold, Robert J.; Prybylowski, Kate; Standley, Steve; Sans, Nathalie; Petralia, Ronald S.

doi:10.1146/annurev.pharmtox.43.100901.135803

Cited by 322 publications

(314 citation statements)

References 136 publications

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“…The developmental switch in NMDA receptor composition from mainly NR1/NR2B to mainly NR1/NR2A was predicted from a number of earlier studies (reviewed by Wenthold et al, 2003). Also, in our previous study (Sans et al, 2000), we showed in immunoblots that NR2B protein decreases and NR2A protein increases with development in hippocampus.…”

Section: Discussionsupporting

confidence: 65%

“…Proteins associated with the PSD can organize into extensive chains beginning with a complex of glutamate receptor-MAGUK-GKAP that can link through GKAP to Shank-Homer and continue to metabotropic GluRs and other proteins Xiao et al, 2000;Wenthold et al, 2003;Ehrengruber et al, 2004). Also, Shank may link directly with the GluRs (mGluR1 and GluRδ2), and indirectly to AMPA receptors via GRIP Uemura et al, 2004).…”

Section: The Shank-homer-mglur Chainmentioning

confidence: 99%

“…Postsynaptic density (PSD) proteins are necessary for excitatory glutamatergic postsynaptic responses, and include scaffolding and functional elements that modulate/mediate signal transduction and trafficking of synaptic proteins (reviewed by Sheng and Kim, 2002;Wenthold et al, 2003;Bredt and Nicoll, 2003;Ehrengruber et al, 2004). In addition to glutamate receptors (GluRs) such as α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and Nmethyl-D-aspartate (NMDA) receptors, numerous other proteins associate with GluRs in the postsynaptic membrane and PSD.…”

Section: Introductionmentioning

confidence: 99%

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Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

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In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluRassociated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors and CaMKII. Other components showed more moderate changes.

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Section: Discussionsupporting

confidence: 65%

Section: The Shank-homer-mglur Chainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ontogeny of postsynaptic density proteins at glutamatergic synapses

Petralia

Sans

Wang

et al. 2005

Molecular and Cellular Neuroscience

Self Cite

206

195

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“…The subunits are assembled cotranslationally in the endoplasmic reticulum, from where they are transported and then inserted at glutamatergic synapses. Release of NMDARs from the endoplasmic reticulum requires phosphorylation of NR1 and NR2 by protein kinases A and C (PKA and PKC), or by serine or tyrosine kinases (Scott et al, 2003;Wenthold et al, 2003). Binding of glutamate or NMDA to synaptic NMDARs allows Ca 2 + into the cell to activate Ca 2 + -dependent enzymes such as calcium/calmodulindependent protein kinase II (CaMKII), PKC, phospholipase Cg, and phospholipase A 2 (PLA 2 ) (Colbran, 2004;Fukunaga et al, 1992;Gurd and Bissoon, 1997;Weichel et al, 1999;Wenthold et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

Basselin

Chang

Bell

et al. 2005

Neuropsychopharmacol

102

131

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It has been proposed that lithium is effective in bipolar disorder (BD) by inhibiting glutamatergic neurotransmission, particularly via N-methyl-D-aspartate receptors (NMDARs). To test this hypothesis and to see if the neurotransmission could involve the NMDARmediated activation of phospholipase A 2 (PLA 2 ), to release arachidonic acid (AA) from membrane phospholipid, we administered subconvulsant doses of NMDA to unanesthetized rats fed a chronic control or LiCl diet. We used quantitative autoradiography following the intravenous injection of radiolabeled AA to measure regional brain incorporation coefficients k* for AA, which reflect receptormediated activation of PLA 2 . In control diet rats, NMDA (25 and 50 mg/kg i.p.) compared with i.p. saline increased k* significantly in 49 and 67 regions, respectively, of the 83 brain regions examined. The regions affected were those with reported NMDARs, including the neocortex, hippocampus, caudate-putamen, thalamus, substantia nigra, and nucleus accumbens. The increases could be blocked by pretreatment with the specific noncompetitive NMDA antagonist MK-801 ((5R,10S)-( + )-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine hydrogen maleate) (0.3 mg/kg i.p.), as well by a 6-week LiCl diet sufficient to produce plasma and brain lithium concentrations known to be effective in BD. MK-801 alone reduced baseline values for k* in many brain regions. The results show that it is possible to image NMDA signaling via PLA 2 activation and AA release in vivo, and that chronic lithium blocks this signaling, consistent with its suggested mechanism of action in BD.

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“…Functional NMDARs are believed to be tetrameric complexes assembled from two GluN1 and two GluN2 (GluN2A-2D) subunits [4,5] . Different NMDAR subtypes have distinct channel properties, such as open probability and time-course of currents [6] .…”

Section: Introductionmentioning

confidence: 99%