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An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability

Author

Listed:
  • Hong-Bo Pang

    (Cancer Research Center, Sanford-Burnham Medical Research Institute)

  • Gary B. Braun

    (Cancer Research Center, Sanford-Burnham Medical Research Institute
    Center for Nanomedicine, Molecular and Developmental Biology, University of California Santa Barbara)

  • Tomas Friman

    (Cancer Research Center, Sanford-Burnham Medical Research Institute
    Center for Nanomedicine, Molecular and Developmental Biology, University of California Santa Barbara)

  • Pedro Aza-Blanc

    (Cancer Research Center, Sanford-Burnham Medical Research Institute)

  • Manuel E. Ruidiaz

    (Cancer Research Center, Sanford-Burnham Medical Research Institute)

  • Kazuki N. Sugahara

    (Cancer Research Center, Sanford-Burnham Medical Research Institute
    Columbia University, College of Physicians and Surgeons)

  • Tambet Teesalu

    (Cancer Research Center, Sanford-Burnham Medical Research Institute
    Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Translational Medicine, University of Tartu)

  • Erkki Ruoslahti

    (Cancer Research Center, Sanford-Burnham Medical Research Institute
    Center for Nanomedicine, Molecular and Developmental Biology, University of California Santa Barbara)

Abstract

Neuropilins (NRPs) are trans-membrane receptors involved in axon guidance and vascular development. Many growth factors and other signalling molecules bind to NRPs through a carboxy (C)-terminal, basic sequence motif (C-end Rule or CendR motif). Peptides with this motif (CendR peptides) are taken up into cells by endocytosis. Tumour-homing CendR peptides penetrate through tumour tissue and have shown utility in enhancing drug delivery into tumours. Here we show, using RNAi screening and subsequent validation studies, that NRP1-mediated endocytosis of CendR peptides is distinct from known endocytic pathways. Ultrastructurally, CendR endocytosis resembles macropinocytosis, but is mechanistically different. We also show that nutrient-sensing networks such as mTOR signalling regulate CendR endocytosis and subsequent intercellular transport of CendR cargo, both of which are stimulated by nutrient depletion. As CendR is a bulk transport pathway, our results suggest a role for it in nutrient transport; CendR-enhanced drug delivery then makes use of this natural pathway.

Suggested Citation

  • Hong-Bo Pang & Gary B. Braun & Tomas Friman & Pedro Aza-Blanc & Manuel E. Ruidiaz & Kazuki N. Sugahara & Tambet Teesalu & Erkki Ruoslahti, 2014. "An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5904
    DOI: 10.1038/ncomms5904
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    Cited by:

    1. Noemi Gioelli & Lisa J. Neilson & Na Wei & Giulia Villari & Wenqian Chen & Bernhard Kuhle & Manuel Ehling & Federica Maione & Sander Willox & Serena Brundu & Daniele Avanzato & Grigorios Koulouras & M, 2022. "Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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