| Abstract |
干扰突触网络广告vocated in the pathogenesis of psychiatric diseases likeschizophrenia. The majority of synaptic proteins involved in neuronal communications are localized in lipid rafts. These rafts form the platform for coordinating neuronal signal transduction, by clustering interacting partners. ThePAG1protein is a transmembrane adaptor protein in the lipid raft signaling cluster that regulates Src family kinases (SFKs), a convergent point for multiple pathways regulating N-methyl-D-aspartate (NMDA) receptors. Reports of de novo missense mutations inPAG1and SFK mediated reductions in tyrosine phosphorylation of NMDA receptor subunit proteins inschizophreniapatients, point to a putative role inschizophreniapathogenesis. To evaluate this, we resequenced the entire coding region ofPAG1in Japaneseschizophreniapatients (n = 1,140) and controls (n = 1,140). We identified eight missense variants, of which four were previously unreported. Case-control genetic association analysis of these variants in a larger cohort (n = 4,182) showed neither a statistically significant association of the individual variants withschizophrenia, nor any increased burden of the rare alleles in the patient group. Expression levels ofPAG1in post-mortem brain samples fromschizophreniapatients and controls also showed no significant differences. To assess the precise role ofPAG1inschizophrenia, future studies with larger sample sizes are needed. |