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Endophilin marks and controls a clathrin-independent endocytic pathway

Author

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  • Emmanuel Boucrot

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK
    Institute of Structural and Molecular Biology, University College London & Birkbeck College, London WC1E 6BT, UK)

  • Antonio P. A. Ferreira

    (Institute of Structural and Molecular Biology, University College London & Birkbeck College, London WC1E 6BT, UK)

  • Leonardo Almeida-Souza

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK)

  • Sylvain Debard

    (Institute of Structural and Molecular Biology, University College London & Birkbeck College, London WC1E 6BT, UK
    Ecole Normale Supérieure de Cachan, 94235 Cachan, France)

  • Yvonne Vallis

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK)

  • Gillian Howard

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK)

  • Laetitia Bertot

    (Institut Pasteur, Unité de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France)

  • Nathalie Sauvonnet

    (Institut Pasteur, Unité de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France)

  • Harvey T. McMahon

    (MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK)

Abstract

Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate—produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2—recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as α2a- and β1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).

Suggested Citation

  • Emmanuel Boucrot & Antonio P. A. Ferreira & Leonardo Almeida-Souza & Sylvain Debard & Yvonne Vallis & Gillian Howard & Laetitia Bertot & Nathalie Sauvonnet & Harvey T. McMahon, 2015. "Endophilin marks and controls a clathrin-independent endocytic pathway," Nature, Nature, vol. 517(7535), pages 460-465, January.
  • Handle: RePEc:nat:nature:v:517:y:2015:i:7535:d:10.1038_nature14067
    DOI: 10.1038/nature14067
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    Cited by:

    1. Wonchul Shin & Ben Zucker & Nidhi Kundu & Sung Hoon Lee & Bo Shi & Chung Yu Chan & Xiaoli Guo & Jonathan T. Harrison & Jaymie Moore Turechek & Jenny E. Hinshaw & Michael M. Kozlov & Ling-Gang Wu, 2022. "Molecular mechanics underlying flat-to-round membrane budding in live secretory cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Hideaki T. Matsubayashi & Jack Mountain & Nozomi Takahashi & Abhijit Deb Roy & Tony Yao & Amy F. Peterson & Cristian Saez Gonzalez & Ibuki Kawamata & Takanari Inoue, 2024. "Non-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Ling-Gang Wu & Chung Yu Chan, 2024. "Membrane transformations of fusion and budding," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Raluca Groza & Kita Valerie Schmidt & Paul Markus Müller & Paolo Ronchi & Claire Schlack-Leigers & Ursula Neu & Dmytro Puchkov & Rumiana Dimova & Claudia Matthaeus & Justin Taraska & Thomas R. Weikl &, 2024. "Adhesion energy controls lipid binding-mediated endocytosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Anabel-Lise Le Roux & Caterina Tozzi & Nikhil Walani & Xarxa Quiroga & Dobryna Zalvidea & Xavier Trepat & Margarita Staykova & Marino Arroyo & Pere Roca-Cusachs, 2021. "Dynamic mechanochemical feedback between curved membranes and BAR protein self-organization," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    6. Samsuzzoha Mondal & Karthik Narayan & Samuel Botterbusch & Imania Powers & Jason Zheng & Honey Priya James & Rui Jin & Tobias Baumgart, 2022. "Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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