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A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors

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  • Stefania Averaimo

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

  • Ahlem Assali

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 839
    INSERM UMR_S 839
    Institut du Fer à Moulin)

  • Oriol Ros

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

  • Sandrine Couvet

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

  • Yvrick Zagar

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

  • Ioana Genescu

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

  • Alexandra Rebsam

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 839
    INSERM UMR_S 839
    Institut du Fer à Moulin)

  • Xavier Nicol

    (Sorbonne Universités, UPMC University Paris 06, UMR_S 968, Institut de la Vision
    CNRS, UMR_7210
    INSERM, UMR_S 968)

Abstract

The development of neuronal circuits is controlled by guidance molecules that are hypothesized to interact with the cholesterol-enriched domains of the plasma membrane termed lipid rafts. Whether such domains enable local intracellular signalling at the submicrometre scale in developing neurons and are required for shaping the nervous system connectivity in vivo remains controversial. Here, we report a role for lipid rafts in generating domains of local cAMP signalling in axonal growth cones downstream of ephrin-A repulsive guidance cues. Ephrin-A-dependent retraction of retinal ganglion cell axons involves cAMP signalling restricted to the vicinity of lipid rafts and is independent of cAMP modulation outside of this microdomain. cAMP modulation near lipid rafts controls the pruning of ectopic axonal branches of retinal ganglion cells in vivo, a process requiring intact ephrin-A signalling. Together, our findings indicate that lipid rafts structure the subcellular organization of intracellular cAMP signalling shaping axonal arbors during the nervous system development.

Suggested Citation

  • Stefania Averaimo & Ahlem Assali & Oriol Ros & Sandrine Couvet & Yvrick Zagar & Ioana Genescu & Alexandra Rebsam & Xavier Nicol, 2016. "A plasma membrane microdomain compartmentalizes ephrin-generated cAMP signals to prune developing retinal axon arbors," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12896
    DOI: 10.1038/ncomms12896
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    Cited by:

    1. Léa Ripoll & Yong Li & Carmen W. Dessauer & Mark Zastrow, 2024. "Spatial organization of adenylyl cyclase and its impact on dopamine signaling in neurons," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Melody Atkins & Maud Wurmser & Michèle Darmon & Fiona Roche & Xavier Nicol & Christine Métin, 2023. "CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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