ArticleProceedings of the National Academy of Sciences of the United States of America2015
FXR1P is a GSK3β substrate regulating mood and emotion processing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Post-transcriptional regulation maintains neurogenic potential of human neural progenitor cells.Stem cell reports · 2026Article
- Comparing loss of individual fragile X proteins suggests strong links to cellular senescence and aging.Cellular and molecular life sciences : CMLS · 2025Article
- An in-depth review of the function of RNA-binding protein FXR1 in neurodevelopment.Cell and tissue research · 2024Review
- Amyloid Properties of the FXR1 Protein Are Conserved in Evolution of Vertebrates.International journal of molecular sciences · 2022Article
- RNA and neuronal function: the importance of post-transcriptional regulation.Oxford open neuroscience · 2022Review
- Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity.Frontiers in molecular neuroscience · 2022Review
- FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors.Molecular psychiatry · 2021Article
- Evidence of an interaction betweenEuropean psychiatry : the journal of the Association of European Psychiatrists · 2021Article
- Fluoxetine regulates eEF2 activity (phosphorylation) via HDAC1 inhibitory mechanism in an LPS-induced mouse model of depression.Journal of neuroinflammation · 2021Article
- AFM and FTIR Investigation of the Effect of Water Flow on Horseradish Peroxidase.Molecules (Basel, Switzerland) · 2021Article
- Advances toward precision medicine for bipolar disorder: mechanisms & molecules.Molecular psychiatry · 2021Review
- Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward.Frontiers in molecular neuroscience · 2021Review
- Fxr1 regulates sleep and synaptic homeostasis.The EMBO journal · 2020Article
- Functional amyloids of eukaryotes: criteria, classification, and biological significance.Current genetics · 2020Review
- Fragile X-related protein family: a double-edged sword in neurodevelopmental disorders and cancer.Critical reviews in biochemistry and molecular biology · 2020Review
- CRISPR-Cas9-Mediated Intersectional Knockout of Glycogen Synthase Kinase 3β in D2 Receptor-Expressing Medial Prefrontal Cortex Neurons Reveals Contributions to Emotional Regulation.The CRISPR journal · 2020Article
- Current challenges and possible future developments in personalized psychiatry with an emphasis on psychotic disorders.Heliyon · 2020Review
- RNA-binding protein FXR1 is presented in rat brain in amyloid form.Scientific reports · 2019Article
- Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability.Human genetics · 2018Article
- Regulation of Adult Neurogenesis by the Fragile X Family of RNA Binding Proteins.Brain plasticity (Amsterdam, Netherlands) · 2018Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 4 countries.
Funding
Abstract
Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.