Functional Consequences of Mutations in Postsynaptic Scaffolding Proteins and Relevance to Psychiatric Disorders

Ting, Jonathan T.; Peça, João; Feng, Guoping

doi:10.1146/annurev-neuro-062111-150442

Cited by 100 publications

(70 citation statements)

References 152 publications

(181 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, associations have been found between schizophrenia and the mGluR5 gene, GRM5, and genes associated with mGluR5 such as those coding for Homer proteins, the postsynaptic density-95 gene, and the regulator of G protein signaling 4, RGS4 (Devon et al, 2001;Ting et al, 2012). The postmortem literature on mGluR5 in schizophrenia is ambiguous.…”

Section: Discussionmentioning

confidence: 99%

Metabotropic glutamate receptor 5 neuroimaging in schizophrenia

Akkus

Treyer

Ametamey

et al. 2017

Schizophrenia Research

View full text Add to dashboard Cite

The metabotropic glutamate receptor 5 (mGluR5) is a promising drug target for the treatment of schizophrenia. In this study, we compared mGluR5 distribution volume ration (DVR) in subjects with schizophrenia and healthy controls. Given our previous findings, we matched samples for gender, age, and smoking status. Binding to mGluR5 was determined using positron emission tomography and [ 11 C]ABP688, which binds to an allosteric site with high selectivity. DVR in the 15 individuals with schizophrenia did not differ from that of the 15 controls. In both groups, smoking was associated with marked global reductions in mGluR5 availability (on average 23.8%). In nonsmoking subjects with schizophrenia, there was a positive correlation between mGluR5 DVR in the medial orbitofrontal cortex and the use of antipsychotic drugs (r = 0.9, p =0.019). Because antipsychotic drugs such as clozapine appeared to have indirect effects on mGluR5 signaling, our findings may be clinically relevant. They also provide promising leads for elucidating the high comorbidity between schizophrenia and tobacco addiction. Low mGluR5 DVR in smokers my represent a risk factor for schizophrenia. Alternatively, smoking may counteract the potential upregulation of mGluR5 by antipsychotic drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Metabotropic glutamate receptor 5 neuroimaging in schizophrenia

Akkus

Treyer

Ametamey

et al. 2017

Schizophrenia Research

View full text Add to dashboard Cite

show abstract

“…Specific NLGN subtypes are located at the postsynaptic membrane of glutamatergic (NLGN1 and NLGN3), GABAergic (NLGN2 and NLGN4) and glycinergic (NLGN4) synapses 25 . The intracellular, carboxy-terminal part of the NLGNs binds to several scaffolding proteins of the postsynaptic density that are encoded by certain ASD-risk genes (Supplementary information S2 (figure)) 105,106 . NLGNs can trigger the formation of glutamatergic and GABAergic synapses, but only in an activity-dependent manner [107][108][109][110] .…”

Section: Translation Post-translational Regulation and Degradationmentioning

confidence: 99%

From the genetic architecture to synaptic plasticity in autism spectrum disorder

2015

View full text Add to dashboard Cite

Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity. Indeed, many of the risk genes that have been linked to these disorders encode synaptic scaffolding proteins, receptors, cell adhesion molecules or proteins that are involved in chromatin remodelling, transcription, protein synthesis or degradation, or actin cytoskeleton dynamics. Changes in any of these proteins can increase or decrease synaptic strength or number and, ultimately, neuronal connectivity in the brain. In addition, when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual's risk for ASD.

show abstract

“…Scaffolding proteins are highly abundant in the postsynaptic density (PSD), in terms of both protein copy numbers and the distinct protein types 155,156 . The role of these scaffolding proteins is connected to neuronal function, and when disrupted, neuronal morphology and synaptic plasticity are subsequently affected, contributing to the etiology of diverse human psychiatric disorders such as schizophrenia, ASD, and obsessivecompulsive spectrum disorders 157 .…”

Section: Synaptic Scaffolding Proteins and Synaptic Vesicle Regulatormentioning

confidence: 99%