A Novel Family of Adhesion-Like Molecules That Interacts with the NMDA Receptor

Wang, Changyu; Chang, Kai; Petralia, Ronald S.; Wang, Yaxian; Seabold, Gail K.; Wenthold, Robert J.

doi:10.1523/jneurosci.3799-05.2006

Cited by 118 publications

(191 citation statements)

References 40 publications

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“…Extracellular domains of NMDAR-and AMPAR-type structures associate with transcleft filaments, which are likely to be adhesion molecules (31,32). Their molecular identities require further investigation.…”

Section: Nmdar-type Structuresmentioning

confidence: 99%

Organization of the core structure of the postsynaptic density

Chen

Winters

Azzam

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

259

274

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Much is known about the composition and function of the postsynaptic density (PSD), but less is known about its molecular organization. We use EM tomography to delineate the organization of PSDs at glutamatergic synapses in rat hippocampal cultures. The core of the PSD is dominated by vertically oriented filaments, and ImmunoGold labeling shows that PSD-95 is a component of these filaments. Vertical filaments contact two types of transmembrane structures whose sizes and positions match those of glutamate receptors and intermesh with two types of horizontally oriented filaments lying 10–20 nm from the postsynaptic membrane. The longer horizontal filaments link adjacent NMDAR-type structures, whereas the smaller filaments link both NMDA- and AMPAR-type structures. The orthogonal, interlinked scaffold of filaments at the core of the PSD provides a structural basis for understanding dynamic aspects of postsynaptic function.

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Section: Nmdar-type Structuresmentioning

confidence: 99%

Organization of the core structure of the postsynaptic density

Chen

Winters

Azzam

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

259

274

View full text Add to dashboard Cite

show abstract

“…NMDA receptors, for example, are linked to the synaptic adhesion protein neuroligin through the PDZ protein PDS-95 and were recently discovered to also interact with a novel family of PDZ domain-containing proteins called synaptic adhesion-like molecules, or SALMs (Wang et al, 2006). Our identification of interactions between the AMPA receptor regulating TARPs and the PDZ protein MAGI-2 expands on this concept.…”

Section: Magi-2 and Neuronal Cell Adhesionmentioning

confidence: 83%

Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain

et al. 2006

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MAGI-2 [also known as S-SCAM (synaptic scaffolding molecule)] is a multi-PDZ domain scaffolding protein that interacts with several different ligands in brain, including PTEN (phosphatase and tensin homolog), dasm1(dendrite arborization and synapse maturation 1), dendrin, axin, ␤-and ␦-catenin, neuroligin, hyperpolarization-activated cation channels, ␤1-adrenergic receptors, and NMDA receptors. We confirmed that MAGI-2 coimmunoprecipitated with stargazin in vivo from mouse cerebral cortex and used in vitro assays to localize the interaction to the C-terminal -TTPV amino acid motif of stargazin and the PDZ1, PDZ3, and PDZ5 domains of MAGI-2. Expression of stargazin recruited MAGI-2 to cell membranes and cell-cell contact sites in transfected HEK-293T cells dependent on the presence of the stargazin -TTPV motif. These experiments identify MAGI-2 as a strong candidate for linking TARP/AMPA receptor complexes to a wide range of other postsynaptic molecules and pathways and advance our knowledge of protein interactions at mammalian CNS synapses.

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“…Furthermore, the protective effects of NR1 may be activity dependent because membrane depolarization was required to activate NMDAR (Vissel et al, 2001). In addition, a recent study indicated that NR1 interacts with synaptic adhesion-like molecules (SALMs) and is involved in neurite outgrowth (Wang et al, 2006). It appears that the expressed NR1 interacts with these SALMs in the presence of LPS, and this facilitates the maintenance of the neurite length.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Inducible Factor-1α Protects Cultured Cortical Neurons from Lipopolysaccharide-Induced Cell Death via Regulation of NR1 Expression

Yeh¹,

Hung²,

Gean³

et al. 2008

J. Neurosci.

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Inflammation is involved in some neurodegenerative disorders. NMDA glutamate receptors play an important role in neuronal development. Here, we show that NR1 expression in the cerebral cortex and primary neurons of rats was upregulated after lipopolysaccharide (LPS) treatment. This increase in NR1 expression was considered to be strongly associated with hypoxia-inducible factor-1␣ (HIF-1␣) activation because the treatment of primary neurons with either echinomycin or small interfering RNA (siRNA) targeting HIF-1␣ could block NR1 expression. HIF-1␣ could be induced by an increase in the translational efficiency of the cells. After this, it was transported into the nucleus where it bound to the NR1 promoter and regulated the induction of NR1 transcriptional activity by LPS. LPS injection into the prefrontal cortex caused neuronal death, and this condition was aggravated by intracerebroventricular injection of echinomycin. Furthermore, knockdown of HIF-1␣ and NR1 by the appropriate siRNAs reduced the neurite outgrowth and viability of the primary neurons. These results suggest that NR1 expression is regulated by HIF-1␣ and plays a protective role in neurons during LPS challenge.

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A Novel Family of Adhesion-Like Molecules That Interacts with the NMDA Receptor

Cited by 118 publications

References 40 publications

Organization of the core structure of the postsynaptic density

Organization of the core structure of the postsynaptic density

Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain

Hypoxia-Inducible Factor-1α Protects Cultured Cortical Neurons from Lipopolysaccharide-Induced Cell Death via Regulation of NR1 Expression

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