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Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis

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Listed:
  • Antonio P. A. Ferreira

    (University College London
    Harvard Medical School)

  • Alessandra Casamento

    (University College London)

  • Sara Carrillo Roas

    (University College London)

  • Els F. Halff

    (University College London
    King’s College London)

  • James Panambalana

    (University College London)

  • Shaan Subramaniam

    (University College London
    Birkbeck College)

  • Kira Schützenhofer

    (University College London)

  • Laura Chan Wah Hak

    (University College London
    University of Oxford)

  • Kieran McGourty

    (University College London
    University of Limerick)

  • Konstantinos Thalassinos

    (University College London)

  • Josef T. Kittler

    (University College London)

  • Denis Martinvalet

    (University of Padova)

  • Emmanuel Boucrot

    (University College London
    Birkbeck College)

Abstract

Endocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low.

Suggested Citation

  • Antonio P. A. Ferreira & Alessandra Casamento & Sara Carrillo Roas & Els F. Halff & James Panambalana & Shaan Subramaniam & Kira Schützenhofer & Laura Chan Wah Hak & Kieran McGourty & Konstantinos Tha, 2021. "Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22603-4
    DOI: 10.1038/s41467-021-22603-4
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