Convergent dopamine and ALK4 signaling to PCBP1 controls FosB alternative splicing and cocaine behavioral sensitization

ABSTRACT: ΔfosB is an alternatively spliced product of the FosB gene that is essential for dopamine-induced reward pathways and which 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

SUBMITTER: Favio, A Krapacher 

PROVIDER: S-SCDT-EMBOJ-2022-110721 | biostudies-other |

REPOSITORIES: biostudies-other