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