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Signaling

Spatial regulation of axonal cAMP

Nature Chemical Biology volume 13, pages 348–349 (2017)Cite this article

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In early-stage developing neurons, the cAMP–PKA (protein kinase A) signaling pathway is strongly inhibited. This negative control is later removed, unleashing cAMP–PKA signaling, particularly in distal axonal parts, thus allowing for axonal growth.

The cAMP–PKA signaling pathway plays an important role in neuronal polarization, neurite outgrowth and pathfinding. This ubiquitous intracellular signaling pathway is involved in a number of cellular functions. The specificity of its action is highly dependent on the isoforms of signaling enzymes participating in this cascade and their physical interactions that determine the formation of subcellular microdomains1. Phosphodiesterases (PDEs) are critical in maintaining this compartmentation, as they interact with scaffolding proteins and promote the local degradation of cAMP, thus efficiently controlling the spread of the cAMP signal around its production site2. Moreover, PDE4 activity is increased upon PKA phosphorylation, thus providing a local negative-feedback system. Gorshkov et al. describe in neurons how such a negative-feedback system is lifted during development, allowing large cAMP responses to be produced in the growing axon3.

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Figure 1: Removal of an AKAP-dependent negative feedback on cAMP during development allows for the production of cAMP responses, with higher efficacy in distal axon.

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Authors and Affiliations

  1. Liliana R Castro and Pierre Vincent are in the Institut de Biologie Paris–Seine, Paris, France and the Université Pierre et Marie Curie, Sorbonne Universités, Paris, France.,

    Pierre Vincent & Liliana R Castro

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  1. Pierre Vincent
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  2. Liliana R Castro
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Correspondence to Pierre Vincent.

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The authors declare no competing financial interests.

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Vincent, P., Castro, L. Spatial regulation of axonal cAMP. Nat Chem Biol 13, 348–349 (2017). https://doi.org/10.1038/nchembio.2339

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