Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: DLG2 - discs, large homolog 2, chapsyn-110...

Homo sapiens

Synonyms: Channel-associated protein of synapse-110, Chapsyn-110, Discs large homolog 2, DKFZp781D1854, DKFZp781E0954, FLJ37266, MGC131811, Postsynaptic density protein PSD-93, PSD-93

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Brenman, J.E., Kristiansen, L.V., Roche, K.W., Leyland, M.L., Zubakov, D., et al.

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Disease relevance of DLG2

NSE, chapsyn 110 and beta SNAP were comparable in the control fetus panel and in Down Syndrome fetuses [1].
Differential expression of a new isoform of DLG2 in renal oncocytoma [2].

High impact information on DLG2

In this issue of Neuron, Elias et al. have elucidated the roles of three MAGUKs, PSD-95, PSD-93, and SAP-102, in the targeting of AMPA receptors to synapses in hippocampal neurons [3].
At immature synapses, PSD-95 and PSD-93 play little role in synaptic AMPA-R clustering; instead, SAP-102 dominates [4].
Chapsyn-110 associates tightly with the postsynaptic density in brain, and mediates the clustering of both NMDA receptors and K+ channels in heterologous cells [5].
In the ultrastructural studies that are described here, PSD-93 localizes to both postsynaptic densities and dendritic microtubules of cerebellar Purkinje neurons [6].
PSD-93 is expressed in discrete neuronal populations as well as in specific non-neuronal cells, and it exhibits complex molecular diversity attributable to tissue-specific alternative splicing [7].

Biological context of DLG2

Yeast two-hybrid screening of a human brain cDNA library using the carboxyl terminus of Kir2.1 as bait yielded cDNA encoding the first two PDZ domains of PSD-93, but with an extended N-terminal region that diverged from other PSD-93 isoforms [8].
RESULTS: We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266 [2].
In addition, PSD-93 clusters delta2 when they are coexpressed in heterologous cells, and clustering is disrupted by point mutations of delta2 that disrupt the delta2-PSD-93 interaction [9].

Anatomical context of DLG2

PSD-93, however, is unique among PSD-95/SAP-90 family members in its expression in Purkinje neuron cell bodies and dendrites [7].
We find that delta2 binds specifically to PSD-93, which is enriched in Purkinje cells [9].

Associations of DLG2 with chemical compounds

Postsynaptic localization of N-methyl-D-aspartate-type glutamate receptors may be mediated by the synapse-associated proteins (SAPs) SAP90, SAP102, and chapsyn-110 [10].

Other interactions of DLG2

We introduced a double mutation (I38A/I40A) into the N-terminal domain of hDlg, which disrupted its interaction with DLG2, a key event in the membrane targeting of hDlg [11].
We found significant changes in the expression of NF-L in DLPFC, and PSD-95 and PSD-93 in ACC; increased transcript expression was associated with decreased protein expression, suggesting abnormal translation and/or accelerated protein degradation of these molecules in schizophrenia [12].
One of these proteins, PSD-93, co-localizes with a subpopulation of nNOS in the macula densa [13].
PSD-93 and beta-catenin are also enriched at alpha3-nAChR postsynaptic sites [14].

References

Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. Weitzdoerfer, R., Dierssen, M., Fountoulakis, M., Lubec, G. J. Neural Transm. Suppl. (2001)
Differential expression of a new isoform of DLG2 in renal oncocytoma. Zubakov, D., Stupar, Z., Kovacs, G. BMC Cancer (2006)
Promiscuous Interactions between AMPA-Rs and MAGUKs. Fitzjohn, S.M., Doherty, A.J., Collingridge, G.L. Neuron (2006)
Synapse-Specific and Developmentally Regulated Targeting of AMPA Receptors by a Family of MAGUK Scaffolding Proteins. Elias, G.M., Funke, L., Stein, V., Grant, S.G., Bredt, D.S., Nicoll, R.A. Neuron (2006)
Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Kim, E., Cho, K.O., Rothschild, A., Sheng, M. Neuron (1996)
Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A. Brenman, J.E., Topinka, J.R., Cooper, E.C., McGee, A.W., Rosen, J., Milroy, T., Ralston, H.J., Bredt, D.S. J. Neurosci. (1998)
Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein. Brenman, J.E., Christopherson, K.S., Craven, S.E., McGee, A.W., Bredt, D.S. J. Neurosci. (1996)
An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. Leyland, M.L., Dart, C. J. Biol. Chem. (2004)
Postsynaptic density-93 interacts with the delta2 glutamate receptor subunit at parallel fiber synapses. Roche, K.W., Ly, C.D., Petralia, R.S., Wang, Y.X., McGee, A.W., Bredt, D.S., Wenthold, R.J. J. Neurosci. (1999)
SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. Leonard, A.S., Davare, M.A., Horne, M.C., Garner, C.C., Hell, J.W. J. Biol. Chem. (1998)
Protein 4.1-mediated membrane targeting of human discs large in epithelial cells. Hanada, T., Takeuchi, A., Sondarva, G., Chishti, A.H. J. Biol. Chem. (2003)
Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia. Kristiansen, L.V., Beneyto, M., Haroutunian, V., Meador-Woodruff, J.H. Mol. Psychiatry (2006)
Protein-protein interactions controlling nitric oxide synthases. Kone, B.C. Acta Physiol. Scand. (2000)
Neuronal nicotinic synapse assembly requires the adenomatous polyposis coli tumor suppressor protein. Temburni, M.K., Rosenberg, M.M., Pathak, N., McConnell, R., Jacob, M.H. J. Neurosci. (2004)