Cooperation of Nuclear Fibroblast Growth Factor Receptor 1 and Nurr1 Offers New Interactive Mechanism in Postmitotic Development of Mesencephalic Dopaminergic Neurons

Abstract

Background: Nurr1 and FGFR1 are integrative nuclear factors participating in postmitotic dopaminergic neuron development. Results: Both nuclear receptors show a functional interaction in co-immunoprecipitation, FRAP, ChIP, and luciferase gene reporter assay. Conclusion: Cooperation of nuclear FGFR1 and Nurr1 offers a new mechanism in transcriptional regulation and integration. Significance: This mechanism may channel diverse stimuli in developing and mature dopaminergic neurons, providing a potential therapeutic target.

Membrane and Integrative Nuclear Fibroblastic Growth Factor Receptor (FGFR) Regulation of FGF-23

“…Indeed, phenylthiohydantoin, which is coupled to both intracellular calcium and cAMP signaling, induces FGF-23 transcription in UMR106 osteoblast-like cells via activation of nuclear receptor-related protein 1 (Nurr1) (53). Our results showing that forskolin alone is insufficient to activate the proximal FGF-23 promoter and that cAMP and HMW-FGF-2 have synergistic effects, and data showing the cooperation of nuclear FGFR1 and Nurr1 in the activation of neuronal genes, such as tyrosine hydroxylase (54), predict that phenylthiohydantoin actions might be influenced by the activity of FGFR1 in bone.…”

Evidence‐Based Theory for Integrated Genome Regulation of Ontogeny—An Unprecedented Role of Nuclear FGFR1 Signaling

“…nFGFR1 forms CBP‐containing low mobility chromatin complexes with RXR, RAR, and Nurs. These complexes bind to RARE, NBRE, and NurRE sequences within RA‐activated Fgfr1, Fgf‐2, and Th genes, and synergistically activate isolated RA‐ and Nur‐responsive elements (Baron et al, 2012; Lee et al, 2012, 2013). …”

Receptor Tyrosine Kinases in the Nucleus

“…There is a report detailing the dynamics of nuclear FGFR1 movement among receptor populations having different motilities taken to represent free receptor or receptor associated with chromatin or nuclear matrix (Dunham-Ems et al 2009). The interaction of FGFR1 and the transcription factor Nurr 1 in the nucleus of dopaminergic neurons has been described (Baron et al 2012). Morphologic studies have recognized FGFR2 in the nucleus of tissue samples (Lu et al 2004;Schmahl et al 2004;Giulianelli et al 2008;Martin et al 2011), but without analysis of the size it is not possible to distinguish whether this represents an intact receptor or a receptor fragment.…”