Binding of Neuroligins to PSD-95

Irie, Mina; Hata, Yoshinobu; Takeuchi, Masami; Ichtchenko, Konstantin; Toyoda, Atsushi; Hirao, Kazuyo; Takai, Yoshimi; Rosahl, Thomas W.; Südhof, Thomas C.

doi:10.1126/science.277.5331.1511

Cited by 687 publications

(553 citation statements)

References 24 publications

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“…cDNA constructs and transfection pGFPN3 PSD-95-1 (Irie et al 1997), -2, and -3, encoding the entire PSD molecule, its Nterminal half, and its C-terminal half, respectively, were kindly provided by Drs Y. Hata and Y. Takai (Osaka University). cDNA transfection of DLD-1 cells was carried out as previously described (Watabe- Uchida et al 1998).…”

Section: Cell Culturesmentioning

confidence: 99%

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

2000

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Section: Cell Culturesmentioning

confidence: 99%

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

2000

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“…Recent studies indicate that ␤-neurexin is synaptically localized and is the axonal receptor of neuroligin-1 (NL1) (6). In addition, NL1 directly interacts with PSD-95 through its C-terminal PDZ-binding motif (9), an interaction that modulates excitatory postsynaptic formation (10)(11)(12). These findings suggest that ␤-neurexin͞NL1 interaction may initiate postsynaptic differentiation by recruiting postsynaptic scaffolding proteins such as PSD-95.…”

mentioning

confidence: 91%

Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter

Nam

Chen

2005

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

292

275

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Presynaptic and postsynaptic differentiation occurs at axodendritic contacts between CNS neurons. Synaptic adhesion mediated by synaptic cell adhesion molecule (SynCAM) and ␤-neurexins͞neu-roligins triggers presynaptic differentiation. The signals that trigger postsynaptic differentiation are, however, unknown. Here we report that ␤-neurexin expressed in nonneuronal cells induced postsynaptic density (PSD)-95 clustering in contacting dendrites of hippocampal neurons. The effect is specific to ␤-neurexin and was not observed with other synaptic cell adhesion molecules such as N-cadherin or SynCAM. NMDA receptors, but not ␣-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors (AMPARs), were recruited to this ␤-neurexin-induced PSD-95 scaffold. Remarkably, AMPARs were inserted into this scaffold upon glutamate application or expression of a constitutively active form of calmodulin kinase II in neurons. Expression of a dominant-negative neuroligin-1 in cultured neurons markedly reduced the sizes and densities of PSD-95 puncta and AMPAR clusters. In addition, excitatory, but not inhibitory, synaptic functions were impaired in these neurons, confirming that PSD-95͞neuroligin-1 interaction is involved in postsynaptic assembly at glutamatergic synapses. These results demonstrate that postsynaptic assembly of the glutamatergic synapse may be initiated by presynaptic ␤-neurexin and that glutamate release also is required for maturation of synapses.␤-neurexin ͉ glutamatergic synapse formation ͉ synaptogenesis I nteractions between presynaptic and postsynaptic neurons are essential for synapse formation (1-5). At glutamatergic synapses in the mammalian CNS, presynaptic differentiation appears to be induced by synaptic adhesion molecules, such as synaptic cell adhesion molecule (SynCAM) and neuroligins (6-8). Mechanisms underlying CNS postsynaptic differentiation are unclear. Although major components of the postsynaptic density (PSD) have been identified, and the sequence of their assembly at nascent glutamatergic synapses has been delineated (1, 3), the axonal signals that induce postsynaptic assembly are still unknown. Recent studies indicate that ␤-neurexin is synaptically localized and is the axonal receptor of neuroligin-1 (NL1) (6). In addition, NL1 directly interacts with PSD-95 through its C-terminal PDZ-binding motif (9), an interaction that modulates excitatory postsynaptic formation (10-12). These findings suggest that ␤-neurexin͞NL1 interaction may initiate postsynaptic differentiation by recruiting postsynaptic scaffolding proteins such as PSD-95.Another potential player in postsynaptic differentiation is neurotransmitter. Observations from Munc18-1-knockout mice suggest that the initial assembly of the synapse, evaluated with ultrastructural morphology and localization of presynaptic proteins, may proceed without neurotransmitter release. However, because postsynaptic receptor localization and function were not evaluated in these mice, whether transmitter release is required for a fully functional postsyn...

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“…The PDZ domain is a protein-interacting module (reviewed in Refs. 9 -12), and PSD-95/SAP90 binds the C termini of N-methyl-D-aspartate (NMDA) receptors, K ϩ channels, neuroligins, synGAP, and CRIPT through distinct PDZ domains to assemble these components at the synaptic junctions (13)(14)(15)(16)(17)(18). PSD-95/SAP90 interacts with SAP90/PSD-95-associated protein (SAPAP) (also called GK-associated protein and hDLGassociated protein) (19 -21), and a recently identified protein, BEGAIN (brain-enriched guanylate kinase-interacting protein) via the GK domain (22).…”

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confidence: 99%

MAGUIN, a Novel Neuronal Membrane-associated Guanylate Kinase-interacting Protein

Yao¹,

Hata²,

Ide³

et al. 1999

Journal of Biological Chemistry

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Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases. Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins, identification of ligands for these proteins is important to elucidate the structure of synaptic junctions. Here, we report a novel protein interacting with the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane-associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile ␣ motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at the plasma membrane via the plekstrin homology domain and the C-terminal region and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domainbinding motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding motif. MAGUINs are expressed in neurons and localized in the cell body and neurites and are coimmunoprecipitated with PSD-95/ SAP90 and S-SCAM from rat crude synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to assemble the components of synaptic junctions.Synaptic junctions are interneuronal cell-cell junctions differentiated for neurotransmission. Neurotransmitters are released from the synaptic vesicles into the synaptic cleft and bind to the receptors accumulated at the postsynapse, opening the ion channels and generating the second messengers involved in synaptic plasticity (reviewed in Ref. 1). The components required for this process are organized at the synaptic junctions to play specific roles in felicitous orders. Several scaffolding proteins are reported to be involved in the assembly of components of synaptic junctions (reviewed in Refs. 2-6). Postsynaptic density (PSD) 1 -95/synapse-associated protein (SAP) 90 has three PSD-95/Dlg-A/ZO-1 (PDZ) domain, one Src homology 3 domain, and one guanylate kinase (GK) domain (7,8). The PDZ domain is a protein-interacting module (reviewed in Refs. 9 -12), and PSD-95/SAP90 binds the C termini of N-methyl-D-aspartate (NMDA) receptors, K ϩ channels, neuroligins, synGAP, and CRIPT through distinct PDZ domains to assemble these components at the synaptic junctions (13-18). PSD-95/SAP90 interacts with SAP90/PSD-95-associated protein (SAPAP) (also called GK-associated protein and hDLGassociated protein) (19 -21), and a recently identified protein, BEGAIN (brain-enriched guanylate kinase-interacting protein) via the GK domain (22). Glutamate receptor-interacting protein has seven PDZ domains and binds ␣ amino-3-hydroxy-5-methyl-4-isoxazaole propionic acid receptors via the fourth and fifth PDZ domains (23). The ligands for other PDZ domains of glutamate receptor-interacting protein have not been so far reported. Synaptic scaffolding molecule (S-SCAM) was originally identified as a SAPAP-interacting protein (24). We have first reported that S-SCAM has one GK, two WW, and five PDZ domains (24). The GK domain of S-SCAM is shorter than that of PSD-95/SAP90. The WW domain is a protein-interacting modul...

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Binding of Neuroligins to PSD-95

Cited by 687 publications

References 24 publications

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Blockade of cadherin‐6B activity perturbs the distribution of PSD‐95 family proteins in retinal neurones

Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter

MAGUIN, a Novel Neuronal Membrane-associated Guanylate Kinase-interacting Protein

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