ArticleThe EMBO journal2022
Convergent dopamine and ALK4 signaling to PCBP1 controls FosB alternative splicing and cocaine behavioral sensitization.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- PCBP1 orchestrates amino acid metabolism burst during the naïve-to-primed pluripotency transition.Stem cell reports · 2026Article
- Morphine and methamphetamine trigger divergent post-transcriptional neuroimmune landscapes in the dorsal striatum.bioRxiv : the preprint server for biology · 2026Article
- Brain-wide induction of ΔFOSB and altered co-activation networks in a rat model for exercise training.Translational psychiatry · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Article
- Alternative splicing in addiction.Current opinion in genetics & development · 2025Review
- Transcriptome analysis identifies EDA1 variants disrupt FOSB-mediated regulation of odontogenic epithelial cell behaviors during dental germ development.Frontiers in cell and developmental biology · 2025Article
- Voluntary Running and Estrous Cycle Modulate ΔFOSB in the Suprachiasmatic Nucleus of the Wistar Rat.Journal of circadian rhythms · 2025Article
- Exploring the potential link between ΔFosB andActa neuropsychiatrica · 2024Review
- Alternative splicing in EMT and TGF-β signaling during cancer progression.Seminars in cancer biology · 2024Review
- It is not just about transcription: involvement of brain RNA splicing in substance use disorders.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Identification of the circRNA-miRNA-mRNA network for treating methamphetamine-induced relapse and behavioral sensitization with cannabidiol.CNS neuroscience & therapeutics · 2024Article
- Genetic loss of the dopamine transporter significantly impacts behavioral and molecular responses to sub-chronic stress in mice.Frontiers in molecular neuroscience · 2024Article
- Conserved role for PCBP1 in altered RNA splicing in the hippocampus after chronic alcohol exposure.Molecular psychiatry · 2023Article
- Intranasal insulin treatment partially corrects the altered gene expression profile in the hippocampus of developing rats with perinatal iron deficiency.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Convergent dopamine and ALK4 signaling to PCBP1 controls FosB alternative splicing and cocaine behavioral sensitization.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ΔfosB is an alternatively spliced product of the FosB gene that is essential for dopamine-induced reward pathways and that acts as a master switch for addiction. However, the molecular mechanisms of its generation and regulation by dopamine signaling are unknown. Here, we report that dopamine D1 receptor signaling synergizes with the activin/ALK4/Smad3 pathway to potentiate the generation of ΔFosB mRNA in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) via activation of the RNA-binding protein PCBP1, a regulator of mRNA splicing. Concurrent activation of PCBP1 and Smad3 by D1 and ALK4 signaling induced their interaction, nuclear translocation, and binding to sequences in exon-4 and intron-4 of FosB mRNA. Ablation of either ALK4 or PCBP1 in MSNs impaired ΔFosB mRNA induction and nuclear translocation of ΔFosB protein in response to repeated co-stimulation of D1 and ALK4 receptors. Finally, ALK4 is required in NAc MSNs of adult mice for behavioral sensitization to cocaine. These findings uncover an unexpected mechanism for ΔFosB generation and drug-induced sensitization through convergent dopamine and ALK4 signaling.
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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.