Proteomics

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The bipolar disorder GWAS risk gene NEK4 modulates circadian fluctuations of murine emotional behaviors and synaptogenesis

ABSTRACT: Through integrative analyses of GWAS summary statistics, population genetic data and expression quantitative trait loci (eQTL) annotations, we found that elevated NEK4 expression in hippocampus was causatively linked to the risk of BD. To examine the biological impact of this gene, we generated NEK4 conditional knock-in mice in pyramidal neurons of the adult forebrain (NEK4 cKI mice) and NEK4 overexpression mice with adeno-associated virus (AAV) mediated in the dorsal hippocampus (NEK4 OE mice). Since NEK4 encodes a serine/threonine kinase, we explored the phosphoproteomic profiles of these mice at different time of the day and compared them with those of the control mice. We isolated the hippocampal proteins of the NEK4 OE mice and the control mice during day and night respectively (n = 3 for each group), and performed phosphorylated 4D-label-free quantitative proteomics analyses. After stringent quality control, 5376 quantifiable phosphorylated peptides were identified in 2415 phosphorylated proteins

ORGANISM(S): Mus <genus>

SUBMITTER: Ming Li  

PROVIDER: PXD052190 | iProX | Sat May 11 00:00:00 BST 2024

REPOSITORIES: iProX

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NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.

Yang Zhi-Hui ZH   Cai Xin X   Zhang Chu-Yi CY   Zhang Qing Q   Li Miao M   Ding Zhong-Li ZL   Guo Yingqi Y   Ma Guolan G   Yang Chao-Hao CH   Guo Lei L   Chang Hong H   Wang Chuang C   Li Ming M   Xiao Xiao X  

Nature communications 20241024 1

GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the do  ...[more]

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