ArticlePLoS medicine2005
Increased expression in dorsolateral prefrontal cortex of CAPON in schizophrenia and bipolar disorder.
Article in PLoS medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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47 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
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- Hepatic nitric oxide synthase 1 adaptor protein regulates glucose homeostasis and hepatic insulin sensitivity in obese mice depending on its PDZ binding domain.EBioMedicine · 2019Article
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- d-Serine administration affects nitric oxide synthase 1 adaptor protein and DISC1 expression in sex-specific manner.Molecular and cellular neurosciences · 2018Article
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- Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.International journal of molecular sciences · 2016Article
- Overexpression of Isoforms of Nitric Oxide Synthase 1 Adaptor Protein, Encoded by a Risk Gene for Schizophrenia, Alters Actin Dynamics and Synaptic Function.Frontiers in cellular neuroscience · 2016Article
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6 authors at 1 institution in 1 country.
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Abstract
backgroundWe have previously reported linkage of markers on chromosome 1q22 to schizophrenia, a finding supported by several independent studies. Within this linkage region, we have identified significant linkage disequilibrium between schizophrenia and markers within the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON). Prior sequencing of the ten exons of CAPON failed to reveal a coding mutation associated with illness. METHODS AND
findingsWe screened a human fetal brain cDNA library and identified a new isoform of CAPON that consists of the terminal two exons of the gene, and verified the expression of the predicted corresponding protein in human dorsolateral prefrontal cortex (DLPFC). We examined the expression levels of both the ten-exon CAPON transcript and this new isoform in postmortem brain samples from the Stanley Array Collection. Quantitative real-time PCR analysis of RNA from the DLPFC in 105 individuals (35 with schizophrenia, 35 with bipolar disorder, and 35 psychiatrically normal controls) revealed significantly (p < 0.005) increased expression of the new isoform in both schizophrenia and bipolar disorder. Furthermore, this increased expression was significantly associated (p < 0.05) with genotype at three single-nucleotide polymorphisms previously identified as being in linkage disequilibrium with schizophrenia.
conclusionBased on the known interactions between CAPON, neuronal nitric oxide synthase (nNOS), and proteins associated with the N-methyl-D-aspartate receptor (NMDAR) complex, overexpression of either CAPON isoform would be expected to disrupt the association between nNOS and the NMDAR, leading to changes consistent with the NMDAR hypofunctioning hypothesis of schizophrenia. This study adds support to a role of CAPON in schizophrenia, produces new evidence implicating this gene in the etiology of bipolar disorder, and suggests a possible mechanism of action of CAPON in psychiatric illness.
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