Neuron
ArticleThe rat brain postsynaptic density fraction contains a homolog of the drosophila discs-large tumor suppressor protein
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2022, American Journal of Human GeneticsCitation Excerpt :For both lines, we found that the mutant iNs showed a marked decrease of both GluA1 and PSD-95 puncta (Figures 4C and 4D), and a concomitant reduction in the density and area of overlapping of GluA1+/PSD-95+ puncta (Figure 4E), compared with wild-type lines. Consistent with the decrease in PSD-95 puncta density and area in the mutant lines, our immunoblotting with PSD-95 antibodies also showed that PSD-95 protein expression (both the 95 kDa and the 70 kDa bands; the lower molecular weight band representing a truncated form of PSD-95 lacking the N terminus57,58) was decreased by approximately 50% in the mutant iNs (Figure 4F). Taken together, our results suggest that the p.Arg89Ter (rs757148409/GenBank: NP_570971.1) mutation identified in our SZ-affected individual is an LoF mutation, reducing dendritic complexity and glutamatergic synapse development in human iNs.