Dlg2

Summary

Gene Symbol: Dlg2
Description: discs large MAGUK scaffold protein 2
Alias: A330103J02Rik, B230218P12Rik, B330007M19Rik, Dlgh2, Gm1197, Gm21505, PSD93, disks large homolog 2, channel-associated protein of synapse-110, chapsyn-110, discs large MAGUK scaffold protein 2 eta, discs large MAGUK scaffold protein 2 gamma, discs, large homolog 2, postsynaptic density protein PSD-93
Species: mouse
Products:     Dlg2

Top Publications

  1. Kim E, Cho K, Rothschild A, Sheng M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron. 1996;17:103-13 pubmed
    ..Thus, chapsyn-110 and PSD-95 may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signalling proteins. ..
  2. Ogawa Y, Horresh I, Trimmer J, Bredt D, Peles E, Rasband M. Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2. J Neurosci. 2008;28:5731-9 pubmed publisher
    ..In contrast, Caspr2, which mediates Kv1 channel clustering at the juxtaparanode, is not required for localization of Kv1 channels at the AIS. These results show PSD-93 mediates AIS accumulation of Kv1 channels independently of Caspr2. ..
  3. Tao Y, Rumbaugh G, Wang G, Petralia R, Zhao C, Kauer F, et al. Impaired NMDA receptor-mediated postsynaptic function and blunted NMDA receptor-dependent persistent pain in mice lacking postsynaptic density-93 protein. J Neurosci. 2003;23:6703-12 pubmed
    ..PSD-93 appears to be important for NMDAR synaptic targeting and function and to be a potential biochemical target for the treatment of persistent pain. ..
  4. Elias G, Funke L, Stein V, Grant S, Bredt D, Nicoll R. Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins. Neuron. 2006;52:307-20 pubmed
    ..These studies establish a PSD-MAGUK-specific regulation of AMPA-R synaptic expression that establishes and maintains glutamatergic synaptic transmission in the mammalian central nervous system. ..
  5. Carlisle H, Fink A, Grant S, O Dell T. Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. J Physiol. 2008;586:5885-900 pubmed publisher
  6. Ogawa Y, Oses Prieto J, Kim M, Horresh I, Peles E, Burlingame A, et al. ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons. J Neurosci. 2010;30:1038-48 pubmed publisher
    ..2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K(+) channel complex that recruits MAGUKs to juxtaparanodes. ..
  7. Horresh I, Poliak S, Grant S, Bredt D, Rasband M, Peles E. Multiple molecular interactions determine the clustering of Caspr2 and Kv1 channels in myelinated axons. J Neurosci. 2008;28:14213-22 pubmed publisher
    ..This mechanism is clearly distinct from the one operating at the axon initial segment, which requires PSD-93 for Kv1 channel clustering. ..
  8. Karnak D, Lee S, Margolis B. Identification of multiple binding partners for the amino-terminal domain of synapse-associated protein 97. J Biol Chem. 2002;277:46730-5 pubmed
    ..We also demonstrate that SAP97 can interact with the MAGUK protein, DLG2, but not the highly related protein, PALS2...
  9. McGee A, Topinka J, Hashimoto K, Petralia R, Kakizawa S, Kauer F, et al. PSD-93 knock-out mice reveal that neuronal MAGUKs are not required for development or function of parallel fiber synapses in cerebellum. J Neurosci. 2001;21:3085-91 pubmed
    ..Our data demonstrate that MAGUK proteins of the PSD-93/95 family are not essential for development of certain central synapses but may instead participate in specialized aspects of synaptic signaling and plasticity. ..

More Information

Publications45

  1. Nada S, Shima T, Yanai H, Husi H, Grant S, Okada M, et al. Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. J Biol Chem. 2003;278:47610-21 pubmed
    ..These results suggest that PSD-93 serves as a membrane-anchored substrate of Fyn and plays a role in the regulation of Fyn-mediated modification of NMDA receptor function. ..
  2. Reggiani C, Coppens S, Sekhara T, DIMOV I, Pichon B, Lufin N, et al. Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability. Genome Med. 2017;9:67 pubmed publisher
    ..and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene...
  3. Frank R, Zhu F, Komiyama N, Grant S. Hierarchical organization and genetically separable subfamilies of PSD95 postsynaptic supercomplexes. J Neurochem. 2017;142:504-511 pubmed publisher
    ..Read the Editorial Highlight for this article on page 500. Cover Image for this issue: doi. 10.1111/jnc.13811. ..
  4. Zhang M, Xu J, Zhu X, Wang Z, Zhao X, Hua Z, et al. Postsynaptic density-93 deficiency protects cultured cortical neurons from N-methyl-D-aspartate receptor-triggered neurotoxicity. Neuroscience. 2010;166:1083-90 pubmed publisher
  5. Parker M, Zhao S, Bredt D, Sanes J, Feng G. PSD93 regulates synaptic stability at neuronal cholinergic synapses. J Neurosci. 2004;24:378-88 pubmed
    ..We find that novel splicing forms of PSD93 (postsynaptic density 93) are expressed in SCG...
  6. Murata Y, Constantine Paton M. Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway. J Neurosci. 2013;33:5040-52 pubmed publisher
    ..Both SAP102 and PAKs are associated with X-linked mental retardation in humans; thus, synapse formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may be crucial for cognitive development. ..
  7. Sato Y, Tao Y, Su Q, Johns R. Post-synaptic density-93 mediates tyrosine-phosphorylation of the N-methyl-D-aspartate receptors. Neuroscience. 2008;153:700-8 pubmed publisher
    ..Our findings indicate that PSD-93 appears to mediate tyrosine-phosphorylation of the NMDA receptors and synaptic localization of Fyn. ..
  8. Fernandez E, Collins M, Uren R, Kopanitsa M, Komiyama N, Croning M, et al. Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Mol Syst Biol. 2009;5:269 pubmed publisher
    ..This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease. ..
  9. Jesaitis L, Goodenough D. Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J Cell Biol. 1994;124:949-61 pubmed
    ..Nagafuchi, S. Tsukita, and Sh. Tsukita. 1991. J. Cell Biol. 115:1449-1462). Thus it appears that ZO-2 is not a component of the fascia adherens, and that unlike ZO-1, this protein is restricted to the epithelial tight junction. ..
  10. Breiderhoff T, Christiansen G, Pallesen L, Vaegter C, Nykjaer A, Holm M, et al. Sortilin-related receptor SORCS3 is a postsynaptic modulator of synaptic depression and fear extinction. PLoS ONE. 2013;8:e75006 pubmed publisher
    ..In conclusion, our studies have identified a novel function for VPS10P domain receptors in control of synaptic depression and suggest SORCS3 as a novel factor modulating aversive memory extinction. ..
  11. Girard B, Merriam L, Tompkins J, Vizzard M, Parsons R. Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture. Am J Physiol Renal Physiol. 2013;305:F1504-12 pubmed publisher
  12. Chenaux G, Matt L, Hill T, Kaur I, Liu X, Kirk L, et al. Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not Formation In Vivo. Eneuro. 2016;3: pubmed
    ..Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampus in vivo. ..
  13. Delint Ramirez I, Fernández E, Bayés A, Kicsi E, Komiyama N, Grant S. In vivo composition of NMDA receptor signaling complexes differs between membrane subdomains and is modulated by PSD-95 and PSD-93. J Neurosci. 2010;30:8162-70 pubmed publisher
    ..These data show critical roles for scaffold proteins and their interactions with NMDA receptor subunits in organizing the differential expression in rafts and postsynaptic densities of synaptic signaling complexes. ..
  14. Shukla A, Beroun A, Panopoulou M, Neumann P, Grant S, Olive M, et al. Calcium-permeable AMPA receptors and silent synapses in cocaine-conditioned place preference. EMBO J. 2017;36:458-474 pubmed publisher
    ..Collectively, our results indicate that CP-AMPAR-mediated maturation of silent synapses in the NAc is a signature of drug-context association, but this maturation is not required for establishing or retaining cocaine-CPP. ..
  15. Ng D, Pitcher G, Szilard R, Sertié A, Kanisek M, Clapcote S, et al. Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning. PLoS Biol. 2009;7:e41 pubmed publisher
  16. Akgul G, Wollmuth L. Expression pattern of membrane-associated guanylate kinases in interneurons of the visual cortex. J Comp Neurol. 2010;518:4842-54 pubmed publisher
  17. Jianhua F, Wei W, Xiaomei L, Shao Hui W. Chronic social defeat stress leads to changes of behaviour and memory-associated proteins of young mice. Behav Brain Res. 2017;316:136-144 pubmed publisher
    ..proteins in the hippocampus were examined, including postsynaptic density 95 (PSD95), postsynaptic density 93 (PSD93), and Protein kinase A (PKA). The levels of PSD95, PSD93, and PKA were significantly lower in susceptible mice...
  18. Nithianantharajah J, Komiyama N, McKechanie A, Johnstone M, Blackwood D, St Clair D, et al. Synaptic scaffold evolution generated components of vertebrate cognitive complexity. Nat Neurosci. 2013;16:16-24 pubmed publisher
    ..carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes...
  19. Kim S, Burette A, Chung H, Kwon S, Woo J, Lee H, et al. NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nat Neurosci. 2006;9:1294-301 pubmed
    ..NGL-2 knockdown reduced excitatory, but not inhibitory, synapse numbers and currents. These results suggest that NGL regulates the formation of excitatory synapses. ..
  20. Lossie A, Nakamura H, Thomas S, Justice M. Mutation of l7Rn3 shows that Odz4 is required for mouse gastrulation. Genetics. 2005;169:285-99 pubmed
    ..Together, our data indicate that Odz4 is mutated in the l7Rn3 allele series and performs roles in the mouse brain, heart, and embryonic patterning similar to those of its Drosophila counterpart. ..
  21. Leyland M, Dart C. An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. J Biol Chem. 2004;279:43427-36 pubmed
    ..We conclude that PSD-93delta is potentially an important regulator of the spatial and temporal distribution of Kir2 channels within neuronal membranes of the central nervous system. ..
  22. Janova H, Arinrad S, Balmuth E, Mitjans M, Hertel J, Habes M, et al. Microglia ablation alleviates myelin-associated catatonic signs in mice. J Clin Invest. 2018;128:734-745 pubmed publisher
    ..Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities. ..
  23. Takei Y, Kikkawa Y, Atapour N, Hensch T, Hirokawa N. Defects in Synaptic Plasticity, Reduced NMDA-Receptor Transport, and Instability of Postsynaptic Density Proteins in Mice Lacking Microtubule-Associated Protein 1A. J Neurosci. 2015;35:15539-54 pubmed publisher
    ..Newly generated mutant mice lacking MAP1A exhibited learning disabilities and reduced synaptic plasticity attributable to disruptions of the anchoring machinery. ..
  24. Christenn M, Kindler S, Schulz S, Buck F, Richter D, Kreienkamp H. Interaction of brain somatostatin receptors with the PDZ domains of PSD-95. FEBS Lett. 2007;581:5173-7 pubmed
    ..As functional parameters of the receptor, such as coupling to potassium channels, are not affected by the interaction with PSD-95, the association may serve to localize the receptor to postsynaptic sites. ..
  25. Karataeva A, Klaassen R, Ströder J, Ruiperez Alonso M, Hjorth J, Van Nierop P, et al. C-terminal interactors of the AMPA receptor auxiliary subunit Shisa9. PLoS ONE. 2014;9:e87360 pubmed publisher
    ..Taken together, our data identifies novel interaction partners of Shisa9, and shows that the C-terminal interactions of Shisa9 through its PDZ domain interaction motif are important for AMPA receptor synaptic and network functions. ..
  26. Sarnyai Z, Jashar C, Olivier B. Modeling combined schizophrenia-related behavioral and metabolic phenotypes in rodents. Behav Brain Res. 2015;276:130-42 pubmed publisher
  27. Zhang Q, Cheng H, Rong R, Yang H, Ji Q, Li Q, et al. The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury. Cell Biochem Biophys. 2015;73:695-700 pubmed publisher
    ..PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia. ..
  28. Krüger J, Favaro P, Liu M, Kitlinska A, Huang X, Raabe M, et al. Differential roles of postsynaptic density-93 isoforms in regulating synaptic transmission. J Neurosci. 2013;33:15504-17 pubmed publisher
    ..Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. ..
  29. Zhang M, Li Q, Chen L, Li J, Zhang X, Chen X, et al. PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia. Neurobiol Dis. 2014;68:104-11 pubmed publisher
    ..These findings may provide a novel avenue for the treatment of ischemic stroke. ..
  30. Duflocq A, Chareyre F, Giovannini M, Couraud F, Davenne M. Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B. BMC Biol. 2011;9:66 pubmed publisher
    ..Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region. ..
  31. Van Campenhout C, Eitelhuber A, Gloeckner C, Giallonardo P, Gegg M, Oller H, et al. Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev Cell. 2011;21:479-91 pubmed publisher
    ..Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation. ..
  32. Tao F, Skinner J, Yang Y, Johns R. Effect of PSD-95/SAP90 and/or PSD-93/chapsyn-110 deficiency on the minimum alveolar anesthetic concentration of halothane in mice. Anesthesiology. 2010;112:1444-51 pubmed publisher
  33. Liaw W, Zhu X, Yaster M, Johns R, Gauda E, Tao Y. Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein. Mol Pain. 2008;4:45 pubmed publisher
    ..The selective effect of PSD-93 deletion on synaptic NMDAR expression in these two major pain-related regions might provide the better strategies for the prevention and treatment of opioid tolerance and physical dependence. ..
  34. Rong R, Yang H, Rong L, Wei X, Li Q, Liu X, et al. Proteomic analysis of PSD-93 knockout mice following the induction of ischemic cerebral injury. Neurotoxicology. 2016;53:1-11 pubmed publisher
    ..Identification of these proteins provides valuable clues to elucidate the mechanisms underlying the actions of PSD-93 in ischemia-reperfusion induced neurotoxicity. ..
  35. Yang J, Seo J, Nair R, Han S, Jang S, Kim K, et al. DGK? regulates presynaptic release during mGluR-dependent LTD. EMBO J. 2011;30:165-80 pubmed publisher
    ..These results suggest that DGK? requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD. ..
  36. Fukaya M, Ueda H, Yamauchi K, Inoue Y, Watanabe M. Distinct spatiotemporal expression of mRNAs for the PSD-95/SAP90 protein family in the mouse brain. Neurosci Res. 1999;33:111-8 pubmed