ArticleBiological psychiatry2019
The Psychiatric Risk Gene NT5C2 Regulates Adenosine Monophosphate-Activated Protein Kinase Signaling and Protein Translation in Human Neural Progenitor Cells.
Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
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- Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions.Nature communications · 2024Article
- Schizophrenia risk proteins ZNF804A and NT5C2 interact in cortical neurons.The European journal of neuroscience · 2024Article
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- Chromosome 10q24.32 Variants Associate with Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.medRxiv : the preprint server for health sciences · 2023Article
- Structural neuroimaging phenotypes and associated molecular and genomic underpinnings in autism: a review.Frontiers in neuroscience · 2023Review
- Genetic map of regional sulcal morphology in the human brain from UK biobank data.Nature communications · 2022Article
- RNA-seq analysis of gene expression profiles in posttraumatic stress disorder, Parkinson's disease and schizophrenia identifies roles for common and distinct biological pathways.Discover mental health · 2022Article
- Transcriptional and Metabolic Investigation in 5'-Nucleotidase Deficient Cancer Cell Lines.Cells · 2021Article
- Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine.Neurochemical research · 2021Article
- Cytosolic 5'-Nucleotidase II Silencing in Lung Tumor Cells Regulates Metabolism through Activation of the p53/AMPK Signaling Pathway.International journal of molecular sciences · 2021Article
- Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.NPJ schizophrenia · 2021Article
- Investigating cytosolic 5'-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr).Translational psychiatry · 2021Article
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe 5'-nucleotidase, cytosolic II gene (NT5C2, cN-II) is associated with disorders characterized by psychiatric and psychomotor disturbances. Common psychiatric risk alleles at the NT5C2 locus reduce expression of this gene in the fetal and adult brain, but downstream biological risk mechanisms remain elusive.
methodsDistribution of the NT5C2 protein in the human dorsolateral prefrontal cortex and cortical human neural progenitor cells (hNPCs) was determined using immunostaining, publicly available expression data, and reverse transcriptase quantitative polymerase chain reaction. Phosphorylation quantification of adenosine monophosphate-activated protein kinase (AMPK) alpha (Thr172) and ribosomal protein S6 (Ser235/Ser236) was performed using Western blotting to infer the degree of activation of AMPK signaling and the rate of protein translation. Knockdowns were induced in hNPCs and Drosophila melanogaster using RNA interference. Transcriptomic profiling of hNPCs was performed using microarrays, and motility behavior was assessed in flies using the climbing assay.
resultsExpression of NT5C2 was higher during neurodevelopment and was neuronally enriched in the adult human cortex. Knockdown in hNPCs affected AMPK signaling, a major nutrient-sensing mechanism involved in energy homeostasis, and protein translation. Transcriptional changes implicated in protein translation were observed in knockdown hNPCs, and expression changes to genes related to AMPK signaling and protein translation were confirmed using reverse transcriptase quantitative polymerase chain reaction. The knockdown in Drosophila was associated with drastic climbing impairment.
conclusionsWe provide an extensive neurobiological characterization of the psychiatric risk gene NT5C2, describing its previously unknown role in the regulation of AMPK signaling and protein translation in neural stem cells and its association with Drosophila melanogaster motility behavior.
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