Human DLG4 blocking peptide

We have determined the cDNA sequence, expression pattern, and chromosomal location of the human gene DLG4, encoding the postsynaptic density-95 (PSD95) protein. hPSD95 is a 723-amino-acid protein that is 99% identical to its rodent counterparts. This is the fourth human protein identified as showing significant similarity to the Drosophila tumor suppressor Dig. These proteins constitute the DLG; subfamily of the membrane-associated guanylate kinase protein family. The expression of DLG4 in neural tissue is consistent with the pattern observed for its rat homolog. However, DLG4 is also expressed in a wide range of nonneural tissues, suggesting that the protein may have additional roles in humans. Using radiation-hybrid mapping panels, we mapped the DLG4 locus to 17p13.1, a region associated with several diseases, the phenotypes of which are consistent with loss of PSD95 function. (C) 1997 Academic Press.

A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since these FDDKI mice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis. After identification by nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass spectrometry, the differentially expressed proteins were classified according to their gene ontology descriptions and their predicted functional interactions. The Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein phosphatases, were revealed by STRING analysis as potential players in the altered synaptic function of FDDKI mice. Immunoblotting analysis finally demonstrated the actual downregulation of the synaptosomal scaffold protein Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes of FDDKI mice.