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Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation

Author

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  • Ryouhei Tsutsumi

    (Kitasato University School of Medicine
    Tohoku University
    NYU Grossman School of Medicine, NYU Langone Health)

  • Beatrix Ueberheide

    (NYU Grossman School of Medicine, NYU Langone Health
    NYU Grossman School of Medicine, NYU Langone Health
    NYU Grossman School of Medicine, NYU Langone Health
    NYU Grossman School of Medicine, NYU Langone Health)

  • Feng-Xia Liang

    (NYU Grossman School of Medicine, NYU Langone Health
    NYU Grossman School of Medicine, NYU Langone Health)

  • Benjamin G. Neel

    (NYU Grossman School of Medicine, NYU Langone Health)

  • Ryuichi Sakai

    (Kitasato University School of Medicine)

  • Yoshiro Saito

    (Tohoku University)

Abstract

Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. Furthermore, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.

Suggested Citation

  • Ryouhei Tsutsumi & Beatrix Ueberheide & Feng-Xia Liang & Benjamin G. Neel & Ryuichi Sakai & Yoshiro Saito, 2024. "Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46971-9
    DOI: 10.1038/s41467-024-46971-9
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    References listed on IDEAS

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    1. Caroline R. Amendola & James P. Mahaffey & Seth J. Parker & Ian M. Ahearn & Wei-Ching Chen & Mo Zhou & Helen Court & Jie Shi & Sebastian L. Mendoza & Michael J. Morten & Eli Rothenberg & Eyal Gottlieb, 2019. "KRAS4A directly regulates hexokinase 1," Nature, Nature, vol. 576(7787), pages 482-486, December.
    2. Ryouhei Tsutsumi & Jana Harizanova & Rabea Stockert & Katrin Schröder & Philippe I. H. Bastiaens & Benjamin G. Neel, 2017. "Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Yvette C. Wong & Daniel Ysselstein & Dimitri Krainc, 2018. "Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis," Nature, Nature, vol. 554(7692), pages 382-386, February.
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