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Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia
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Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia
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Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia
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Journal Article
Sequencing and expression analyses of the synaptic lipid raft adapter gene PAG1 in schizophrenia
2015
Overview
Disruption of synaptic networks has been advocated in the pathogenesis of psychiatric diseases like schizophrenia. 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. The PAG1 protein 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 in
PAG1
and SFK mediated reductions in tyrosine phosphorylation of NMDA receptor subunit proteins in schizophrenia patients, point to a putative role in schizophrenia pathogenesis. To evaluate this, we resequenced the entire coding region of
PAG1
in Japanese schizophrenia patients (
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 with schizophrenia, nor any increased burden of the rare alleles in the patient group. Expression levels of
PAG1
in post-mortem brain samples from schizophrenia patients and controls also showed no significant differences. To assess the precise role of
PAG1
in schizophrenia, future studies with larger sample sizes are needed.
Publisher
Springer Vienna,Springer Nature B.V
