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Dendritic geometry shapes neuronal cAMP signalling to the nucleus

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  • Lu Li

    (Inserm, UMR-S 839
    Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités
    Institut du Fer à Moulin
    Present address: The Babraham Institute, Cambridge CB22 3AT, UK)

  • Nicolas Gervasi

    (Inserm, UMR-S 839
    Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités
    Institut du Fer à Moulin)

  • Jean-Antoine Girault

    (Inserm, UMR-S 839
    Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités
    Institut du Fer à Moulin)

Abstract

Neurons have complex dendritic trees, receiving numerous inputs at various distances from the cell body. Yet the rules of molecular signal propagation from dendrites to nuclei are unknown. DARPP-32 is a phosphorylation-regulated signalling hub in striatal output neurons. We combine diffusion-reaction modelling and live imaging to investigate cAMP-activated DARPP-32 signalling to the nucleus. The model predicts maximal effects on the nucleus of cAMP production in secondary dendrites, due to segmental decrease of dendrite diameter. Variations in branching, perikaryon size or spines have less pronounced effects. Biosensor kinase activity measurement following cAMP or dopamine uncaging confirms these predictions. Histone 3 phosphorylation, regulated by this pathway, is best stimulated by cAMP released in secondary-like dendrites. Thus, unexpectedly, the efficacy of diffusion-based signalling from dendrites to nucleus is not inversely proportional to the distance. We suggest a general mechanism by which dendritic geometry counterbalances the effect of dendritic distance for signalling to the nucleus.

Suggested Citation

  • Lu Li & Nicolas Gervasi & Jean-Antoine Girault, 2015. "Dendritic geometry shapes neuronal cAMP signalling to the nucleus," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7319
    DOI: 10.1038/ncomms7319
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