Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

Ana-Citlali Gradilla, Esperanza González, Irene Seijo, German Andrés, Marcus Bischoff, Laura González-Mendez, Vanessa Sánchez, Ainhoa Callejo, Carmen Ibáñez, Milagros Guerra, João Ramalho Ortigão-Farias, James D. Sutherland, Monika González, Rosa Barrio, Juan M. Falcón-Pérez () and Isabel Guerrero ()
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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
Isabel Guerrero: Centro de Biología Molecular ‘Severo Ochoa’ (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6649

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