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Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

Author

Listed:
  • Ana-Citlali Gradilla

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Esperanza González

    (CIC bioGUNE, Bizkaia Technology Park)

  • Irene Seijo

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • German Andrés

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Marcus Bischoff

    (University of St Andrews, Biomedical Sciences Research Complex, North Haugh, St Andrews)

  • Laura González-Mendez

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Vanessa Sánchez

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Ainhoa Callejo

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Carmen Ibáñez

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • Milagros Guerra

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • João Ramalho Ortigão-Farias

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

  • James D. Sutherland

    (CIC bioGUNE, Bizkaia Technology Park)

  • Monika González

    (CIC bioGUNE, Bizkaia Technology Park)

  • Rosa Barrio

    (CIC bioGUNE, Bizkaia Technology Park)

  • Juan M. Falcón-Pérez

    (CIC bioGUNE, Bizkaia Technology Park
    IKERBASQUE, Basque Foundation for Science
    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Bizkaia Technology Park)

  • Isabel Guerrero

    (Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco)

Abstract

The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.

Suggested Citation

  • Ana-Citlali Gradilla & Esperanza González & Irene Seijo & German Andrés & Marcus Bischoff & Laura González-Mendez & Vanessa Sánchez & Ainhoa Callejo & Carmen Ibáñez & Milagros Guerra & João Ramalho Or, 2014. "Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6649
    DOI: 10.1038/ncomms6649
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    Cited by:

    1. Adrián Aguirre-Tamaral & Manuel Cambón & David Poyato & Juan Soler & Isabel Guerrero, 2022. "Predictive model for cytoneme guidance in Hedgehog signaling based on Ihog- Glypicans interaction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Fabian Gude & Jurij Froese & Dominique Manikowski & Daniele Di Iorio & Jean-Noël Grad & Seraphine Wegner & Daniel Hoffmann & Melissa Kennedy & Ralf P. Richter & Georg Steffes & Kay Grobe, 2023. "Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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