What is it about?

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.

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Why is it important?

These findings uncover an unexpected mechanism for ΔFosB generation and drug-induced sensitization through convergent dopamine and ALK4 signaling.


The current view is that ΔFosB mRNA is generated constitutively above a certain level of FosB mRNA expression. According to this model, the machinery that promotes the alternative splicing of FosB mRNA is not thought to be affected or regulated by dopamine signaling. In the present study, we describe a previously unknown mechanism by which dopamine signaling synergizes with the TGFβ superfamily receptor ALK4 to potentiate the production of ΔFosB in MSNs of the NAc through activation of the RNA-binding protein PCBP1

PhD Favio Krapacher
Karolinska Institutet

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This page is a summary of: Convergent dopamine and ALK4 signaling to PCBP1 controls FosB alternative splicing and cocaine behavioral sensitization, The EMBO Journal, June 2022, EMBO,
DOI: 10.15252/embj.2022110721.
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